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Lu M.,Hubei University of Chinese Medicine | Lu M.,China Three Gorges University | Lu M.,Yichang Central Peoples Hospital | Lu H.,Central Hospital of Wuhan | And 3 more authors.
Expert Review of Anticancer Therapy | Year: 2015

Prostate cancer (PCa) is the second leading cause of cancer-related death in men. Androgen receptor has a key role in the initiation and progression of PCa. Currently, androgen deprivation therapy is the standard treatment for PCa patients due to its effective suppression of androgen receptor signaling. Even though androgen deprivation therapy shows its initial effectiveness on shrinking tumor size, it eventually fails to cure advanced PCa, which is determined by the occurrence of castration-resistance. In this review, we summarize the widely accepted mechanisms that account for castration-resistant PCa and discuss potential therapeutic targets. © 2015 Informa UK Ltd.

Wu T.,Central Hospital of Wuhan | Wu T.,Hubei University of Chinese Medicine | Chen W.,Central Hospital of Wuhan | Chen W.,Cancer Research Institute of Wuhan | And 13 more authors.
FEBS Letters | Year: 2014

Various studies have reported that Huaier possesses anti-tumor effects. However, the mechanisms are not completely elucidated. Here, we found 66 differentially expressed miRNAs in Huaier-treated pulmonary adenocarcinoma A549 cells, with upregulation of miR-26b-5p. Transfection of A549 cells with miR-26b-5p mimic inhibited proliferation and induced apoptosis, while transfection of Huaier-treated A549 cells with a miR-26b-5p inhibitor reversed the effects of Huaier. EZH2 was verified as the target of miR-26b-5p. Thus, our findings indicate that Huaier might suppress proliferation and induce apoptosis in lung cancer cells via a miR-26b-5p-EZH2-mediated approach, which provides a new perspective for understanding the anti-tumor effects of Huaier. © 2014 The Authors. Published by Elsevier B.V.

Lu H.,Central Hospital of Wuhan | Lu H.,Cancer Research Institute of Wuhan | Lei Z.,Central Hospital of Wuhan | Lei Z.,Cancer Research Institute of Wuhan | And 10 more authors.
Oncology Reports | Year: 2013

Telomeres are the end structures of chromosomes in mammalian cells; they play a pivotal role in maintaining the stability of the chromosome and become shorter with each cell division. However, several types of tumor cells express telomerase in very high levels to overcome this crisis and achieve the ability to proliferate endlessly. The telomerase inhibitors can partly inhibit tumor cell proliferation and promote apoptosis, but their roles are only limited. Tankyrase is a poly(ADP-ribose) polymerase which has synergistic effect on telomerase, and is expressed in lung cancer cells in high levels. In the present study, antisense oligonucleotides of telomerase (ashTERT) and tankyrase (asTANKS) were used as specific inhibitors to silence the expression of target genes in A549 human lung adenocarcinoma cells by transfection. The results showed that ashTERT and asTANKS suppressed the expression of telomerase and tankyrase significantly; both inhibited the activity of telomerase and the combination group achieved better effect, but only ashTERT shortened the length of telomeres, asTANKS did not. Further studies showed that ashTERT and asTANKS-promoted A549 apoptosis was not mediated by downregulation of the expression of the anti-apoptotic gene BCL-2 or upregulation of the expression of the pro-apoptotic gene BAX, but by adjusting the two isoforms proportion of myeloid cell leukemia-1 (MCL-1) which can interact with tankyrase directly. MCL-1short (MCL-1S), a pro-apoptotic gene, increased more than MCL-1Long (MCL-1L) which is an anti-apoptotic gene, leading to A549 cell apoptosis and a similar result was obtained in nude mice in vivo. The present study suggests that combination of the inhibitors of telomerase and tankyrase can be used as a strategy for the treatment of lung cancer in humans.

Kong D.,Central Hospital of Wuhan | Chen H.,Central South University | Chen W.,Central Hospital of Wuhan | Chen W.,Cancer Research Institute of Wuhan | And 11 more authors.
European Journal of Medical Research | Year: 2013

Abstract. Background: Primary hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. However, the molecular pathogenesis of HCC is not well-understood, and the prognosis for patients with HCC remains very poor. Methods. To disclose detailed genetic mechanisms in hepatocellular carcinoma (HCC) with a view toward development of novel therapeutic targets, we analyzed expression profiles HCCs and their corresponding noncancerous tissues by using bioinformatics method. Results: In this paper, we report the identification of genes whose expression has been altered and the changed bio-pathways during hepatocarcinogenesis. Hepatoma cells infect intracellular and intercellular signal transduction through Focal adhesion and cause abnormal expression of important intracellular signaling pathway. In addition, it is worth mentioning that some small molecules still restored to the state similar to normal cells, such as bambuterol and lovastatin. This member gene set would serve as a pool of lead gene targets for the identification and development of novel diagnostic and therapeutic biomarkers to greatly improve the clinical management of HCC patients with different risks of recurrence after curative partial hepatectomy. Conclusions: The study has great significance for gene therapy and pharmacotherapy and provides a new treatment entry point and a potential new clinical drug for HCC patients. © 2013 Kong et al.; licensee BioMed Central Ltd.

Lu C.,Central Hospital of Wuhan | Lu C.,Cancer Research Institute of Wuhan | Huang T.,Central Hospital of Wuhan | Huang T.,Cancer Research Institute of Wuhan | And 3 more authors.
Oncology Reports | Year: 2015

Lung cancer is the leading cause of cancer-related mortality in humans. Exploration of the mechanisms underlying the self-renewal and stemness maintenance of cancer stem-like cells (CSLCs) will open new avenues in lung cancer diagnosis and therapy. Here, we isolated and identified a subpopulation of lung cancer stem-like cells (LCSLCs) from non-small cell lung carcinoma (NSCLC) A549 cells with features including self-renewal capacity in vitro, elevated tumorigenic activity in vivo, and high expression of stemness markers CD44, CD133, aldehyde dehydrogenase 1 (ALDH1) and Sox2, using a serum-free suspension sphere-forming culture method. We then found a higher expression level of gonadotropin-releasing hormone (GnRH) in the LCSLCs using a microarray assay, suggesting that GnRH may play a role in the self-renewal capacity and stemness maintenance in lung cancer cells. In addition, the suppression of GnRH capacity negatively regulated self-renewal and stemness maintenance in the LCSLCs. Overexpression of GnRH promoted stemness properties of A549-derived LCSLCs, indicating that GnRH expression is essential for the self-renewal and stemness maintenance in LCSLCs. Moreover, further investigations demonstrated that the promotion of GnRH functions of self-renewal and stemness maintenance in LCSLCs was associated with the JNK signaling pathway. Therefore, our results showed that GnRH participates in the self-renewal capacity and stemness maintenance of LCSLCs by upregulating the JNK signaling pathway, and GnRH may be useful as an alternative LCSLC therapy. © 2015, Spandidos Publications. All rights reserved.

Chen W.,Central Hospital of Wuhan | Chen W.,Cancer Research Institute of Wuhan | Wang H.,Central Hospital of Wuhan | Chen H.,Central South University | And 11 more authors.
European Journal of Haematology | Year: 2014

Background: Expression patterns of microRNAs in serum are involved in potentially non-invasive biomarkers for various diseases. The purpose of this study is to examine the expression of miR-21 in serum of patients with diffuse large B-cell lymphoma (DLBCL) and to validate the significance of miR-21 in early diagnosis, genotyping, treatment options as well as its prognosis estimates of Chinese DLBCL. Methods: miR-21 expression was detected by fluorescent quantity polymerase chain reaction (qPCR) in 9 DLBCL cell lines (OCI-Ly1, OCI-Ly3, OCI-Ly4, OCI-Ly7, OCI-Ly8, OCI-Ly10, OCI-Ly18, OCI-Ly19, and HBL), as well as in tumor tissue and serum samples from patients with DLBCL (germinal center B-cell-like (GCB) DLBCL 32; activated B-cell-like (ABC) DLBCL 30) and 50 healthy subjects. Results: Expression of miR-21 was increased in DLBCL cell lines. Compared with the miR-21 expression of GCB subgroup (OCI-Ly1, OCI-Ly4, OCI-Ly7, OCI-Ly8, OCI-Ly18, OCI-Ly19), ABC subgroup (OCI-Ly3, OCI-Ly10, and HBL) has higher expression (t = 11.18, P < 0.01). Circulating miR-21 level in sera from patients with DLBCLwas associated with matched tumor tissue (r2 = 0.931, P < 0.0001). Consistent with the in vitro, miR-21 expression levels in serum of patients with DLBCL [21.38(10.26-45.21)] were higher than those in serum of control cases [1.87(1.05-3.97); U = 168, P = 0.000]. Moreover, miR-21 expression levels in serum of patients with subgroup ABC [28.68(14.92~98.44)] were higher than that of patients with subgroup GCB [18.3(7.32~33.46); U = 336, P = 0.043]. miR-21 expression in serum of DLBCL with stage I and II were higher than those in stage III and IV (U = 62, P = 0.013 in GCB type; U = 53, P = 0.014 in ABC type). Compared with relapse-free survival in patients with DLBCL, high expression of miR-21 was associated with well prognosis (U = 259, P = 0.035). Conclusion: miR-21 expressed in the serum of patients with DLBCL from Chinese was associated with clinical stage, molecular subgroup, and prognosis estimates. miR-21 may be served as a biomarker in early diagnosis, genotyping, treatment options, and prognosis estimating of Chinese DLBCL. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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