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Chen M.,Harbin Medical University | Liu Y.,Harbin Medical University | Yi D.,Harbin Medical University | Wei L.,Harbin Medical University | And 3 more authors.
Cellular Physiology and Biochemistry | Year: 2014

Background: Tanshinone IIA inhibits the proliferation of pulmonary artery smooth muscle cells (PASMCs), but the potential mechanisms of its effects on PASMCs apoptosis remain unclear. Methods: Rat were subjected to hypoxia for 9 days with or without Tanshinone IIA treatment. PASMCs were exposed to the conditions of 2% O2 and 93% N2 for 24 h in vitro. Hematoxylin and eosin (HE) staining was used to evaluate vascular remodeling. The Cell viability was determined using cell fluorescence staining and MTT assays, and apoptosis was assessed using flow cytometry. Protein expression was quantified by Western blotting. Results: Our results showed that Tanshinone IIA treatment reduced pulmonary artery media thickening in hypoxic rats. Tanshinone IIA reduced PASMC viability in a dose-dependent manner. Additionally, Tanshinone IIA promoted PASMC apoptosis, lowered Hsp60 levels, and upregulated caspase-3 expressions under hypoxic conditions. This pro-apoptotic effect of Tanshinone IIA might be due to the reduction of the phosphorylation of JAK2/STAT3 signaling markers and the increase in the levels of the downstream target, Cx43 in PASMCs. Conclusion: These data suggest that Tanshinone IIA promotes PASMC apoptosis during hypoxia and reverses vascular remodeling. This effect is mediated by modulating the expression of Hsp60, caspase-3, and Cx43 via the JAK2/STAT3 signaling pathway. These results might provide a new therapeutic target to explore a novel strategy for hypoxia-induced vessel remodeling. © 2014 S. Karger AG, Basel.

Liang X.,Harbin Medical University | Sun S.,Harbin Medical University | Zhang X.,Harbin Medical University | Wu H.,Harbin Medical University | And 6 more authors.
Cancer Science | Year: 2015

The aim of this study is to investigate the expression of ribosome-binding protein 1 (RRBP1) in invasive breast cancer and to analyze its relationship to clinical features and prognosis. RRBP1 expression was studied using real-time quantitative PCR and western blotting using pair-matched breast samples and immunohistochemical staining using a tissue microarray. Then the correlation between RRBP1 expression and clinicopathologic features was analyzed. RRBP1 mRNA and protein expression were significantly increased in breast cancer tissues compared with normal tissues. The protein level of RRBP1 is proved to be positively related to histological grade (P = 0.02), molecular subtype (P = 0.048) and status of Her-2 (P = 0.026) and P53 (P = 0.015). We performed a grade-stratified analysis of all patients according to the level of RRBP1 expression and found that RRBP1 overexpression highly affected overall survival in patients with early-stage (I and II) tumors (P = 0.042). Furthermore, Her-2 positive patients with negative RRBP1 expression had longer overall survival rates than those with positive RRBP1 expression (P = 0.031). Using multivariate analysis, it was determined that lymph node metastasis (LNM, P = 0.002) and RRBP1 expression (P = 0.005) were independent prognosis factors for overall survival. RRBP1 is a valuable prognostic factor in Her-2-positive breast cancer patients, indicating that RRBP1 is a potentially important target for the prediction of prognosis. RRBP1 is a valuable prognostic factor in Her-2 positive breast cancer patients, indicating RRBP1 may be a potentially important target for the prediction of prognosis. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Li C.,Harbin Medical University | Cai S.,Fudan University | Wang X.,Harbin Medical University | Wang X.,Heilongjiang Academy of Medical science | And 2 more authors.
PLoS ONE | Year: 2014

Background and Objectives: Transcription factor 3 (TCF3) implicates Wnt signaling pathway and regulates E-cadherin expression, which is involved in aggressiveness of tumors. This study aims to investigate the role of TCF3 in predicting prognosis of patients with stage II and III colorectal cancer (CRC). Copyright:Methods: Real-Time quantitative PCR was performed in 64 fresh CRC tissues and 6 cell lines to examine TCF3 mRNA expression. TCF3 protein expression dynamics were detected by immunohistochemistry of 118 paraffin-embedded specimens, and the clinical significance of TCF3 was assessed by clinical correlation and Kaplan-Meier analyses. Aberrant hypomethylation of TCF3 promoter was also investigated using bisulfite sequencing and methylation specific PCR.Results: The up-regulation of TCF3 mRNA was frequently detected both in CRC tissues with recurrence and metastasisderived cell lines. The expression level of TCF3 protein was significantly correlated with histological type (P = 0.038) and disease-free survival time (P = 0.002). Higher TCF3 expression indicated poor prognostic outcomes (P<0.05, log-rank test). Multivariate analysis also showed strong TCF3 protein expression and perineural invasion were independent adverse prognosticators in CRC (P= 0.010, 0.000). Moreover, it was showed that promoter hypomethylation of TCF3 is associated with its up-expression.Conclusions: This study highlighted the prognostic value of TCF3 in stage II and III CRC. The up-regulation of TCF3, which is mainly caused by promoter hypomethylation, is one of the molecular mechanisms involved in the development and progression of CRC. © 2014 Li et al.

Jiang Z.,Heilongjiang Academy of Medical science | Jiang Z.,Harbin Medical University | Muhammad S.,Harbin Medical University | Wang X.,Heilongjiang Academy of Medical science | Wang X.,Harbin Medical University
Chinese Journal of Cancer Research | Year: 2013

It is well known that one-stage resection of synchronous multiple primary colorectal carcinoma is an ideal choice if the patient's physical condition is not bad. Detailed examination of the whole intestinal tract is very important for patients with colorectal cancer, which could prevent patients from receiving repeat treatment to a great extent. We present a case report of a patient with synchronous primary colorectal cancer. Because pre- or intra-operative examination is not sufficient at his first consultation, the patient had undergone multiple operations after receiving chemotherapy, radiotherapy and intestinal stent insertion, which results in peritoneal adhesions formation. The preoperative placement of prophylactic ureteral catheters facilitated recognition of ureters in operation that assure the prevention of ureteral injuries. If not aware of the importance of detailed preoperative examination and standardized treatment can lead to wrong treatment as in this case. Prophylactic ureteral catheters might assist in their immediate recognition. © Chinese Journal of Cancer Research. All rights reserved.

Xu S.,Harbin Medical University | Sui S.,Harbin Medical University | Zhang J.,Harbin Medical University | Bai N.,Harbin Medical University | And 9 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2015

The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) regulates cell motility via the transcriptional or post-transcriptional control of motility-related genes. Whether MALAT1 plays a critical role in cancer progression in breast cancer remains unclear. In this study, we found that MALAT1 was downregulated in breast tumor cell lines and cancer tissue, and showed that knockdown of MALAT1 in breast cancer cell lines induced an epithelial-to-mesenchymal transition (EMT) program via phosphatidylinositide-3 kinase-AKT pathways. Furthermore, lower expression of MALAT1 in breast cancer patients was associated with shorter relapse-free survival. Thus, our results indicate for the first time that MALAT1 is a novel regulator of EMT in breast cancer and may be a potential therapeutic target for breast cancer metastasis.

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