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Wu J.,The Affiliated Hospital of Guangdong Medical University | Hu L.,Guangdong Medical University | Chen M.,The Affiliated Hospital of Guangdong Medical University | Cao W.,Guangdong Medical University | And 2 more authors.
OncoTargets and Therapy | Year: 2016

Purpose: The expression of pyruvate kinase M2 (PKM2) has been linked to tumor formation and invasion. Specifically, the relationship between high PKM2 expression and prognosis has been evaluated in solid tumors of digestive system. However, the prognostic value of PKM2 remains controversial. Methods: A literature search of PubMed, Embase, and Cochrane databases was conducted until October 2015. The end point focused on overall survival (OS). The pooled hazard ratio (HR) or odds ratio and the 95% confidence intervals were calculated to correlate PKM2 overexpression with OS and clinicopathological characteristics by employing fixed-or random-effects models, depending on the heterogeneity of the included studies. Results: We identified 18 cohorts in 16 studies involving 2,812 patients for this meta-analysis. Overall, the combined HR for OS in all tumor types was 1.74 (1.44-2.11; P<0.001). When stratified by tumor type, the influence of PKM2 expression on poor prognosis was also found in gastric cancer (HR =1.54 [1.08-2.21], P=0.018), esophageal squamous cell carcinoma (HR =1.71 [1.38-2.12], P<0.001), hepatocellular cancer (HR =1.92 [1.52-2.42], P<0.001), biliary cancer (HR =2.11 [1.50-2.95], P<0.001), and oral cancer (HR =3.49 [1.97-6.18], P<0.001), but not in pancreatic ductal adenocarcinoma (HR =1.03 [0.28-3.76], P=0.968). Furthermore, PKM2 overexpression had a negative effect on the late clinical stage of all tumor types except for pancreatic ductal adenocarcinoma. The high density of PKM2 overexpression was significantly associated with some clinical characteristics in different cancer types, such as tumor stage, modal metastasis, and tumor size. Conclusion: Our findings revealed significant association of PKM2 overexpression with OS and certain clinicopathological features in solid tumors of digestive system, thereby suggesting that PKM2 might be an indicator of poor prognosis in digestive system cancers. © 2016 Wu et al. Source

Zhou M.,Guangdong Medical University | Zheng Y.,The Affiliated Hospital of Guangdong Medical University | Li J.,Guangdong Medical University | Wu J.,Guangdong Medical University | And 4 more authors.
Experimental and Therapeutic Medicine | Year: 2016

Osteoporosis (OP), which is a common bone disease associated with reduced bone mineral density and disordered bone microstructure, may result in an increased risk of bone fracture. The present study aimed to investigate the frequency of alendronate (Aln)‑associated upper gastrointestinal tract adverse events (GIAEs) in postmenopausal women with OP. The following databases were searched in order to identify relevant studies: Medline (using PubMed as the search engine), Embase, the Web of Science and the Cochrane Central Register of Controlled Trials (up to December 2014). Studies were selected for inclusion if they were randomized, double‑blind, placebo‑controlled trials, which had investigated the safety of Aln versus a placebo for the treatment of postmenopausal women with OP. The primary outcomes of the included studies were total adverse events (AEs) and upper GIAEs, whereas individual upper GIAEs were considered as secondary outcomes. The general characteristics and outcomes of each study were abstracted by two independent researchers, and Review Manager 5.3 software was used for data syntheses and the meta‑analysis. A total of nine studies, including 15,192 randomized patients, met the inclusion criteria and contributed to some or all of the meta‑analysis outcomes. The Mantel‑Haenszel method was used to calculate risk ratios, and their 95% confidence intervals (CI) were determined using either the fixed or random effects model, depending on the level of heterogeneity. The relative risk (95% CI) of AEs associated with Aln treatment, as compared with the placebo group, was 1.01 (0.97‑1.06), and the relative risk (95% CI) of discontinued Aln treatment due to AEs was 1.04 (0.91‑1.19). In addition, the relative risk (95% CI) of upper GIAEs was 1.02 (0.99‑1.06), and the relative risk (95% CI) of discontinued Aln treatment due to upper GIAEs was 1.23 (0.97‑56). In addition, these results remained robust to sensitivity analyses. The results of the present study suggested that Aln has a good GI tract tolerability, and that daily treatment with 10 mg Aln sodium does not increase the risk of GIAEs in postmenopausal women with OP. © 2016, Spandidos Publications. All rights reserved. Source

Wu W.,The Affiliated Hospital of Guangdong Medical University | Lin C.,The Affiliated Hospital of Guangdong Medical University | Wu K.,The Affiliated Hospital of Guangdong Medical University | Jiang L.,The Affiliated Hospital of Guangdong Medical University | And 20 more authors.
EMBO Journal | Year: 2016

In hypoxic cells, dysfunctional mitochondria are selectively removed by a specialized autophagic process called mitophagy. The ER–mitochondrial contact site (MAM) is essential for fission of mitochondria prior to engulfment, and the outer mitochondrial membrane protein FUNDC1 interacts with LC3 to recruit autophagosomes, but the mechanisms integrating these processes are poorly understood. Here, we describe a new pathway mediating mitochondrial fission and subsequent mitophagy under hypoxic conditions. FUNDC1 accumulates at the MAM by associating with the ER membrane protein calnexin. As mitophagy proceeds, FUNDC1/calnexin association attenuates and the exposed cytosolic loop of FUNDC1 interacts with DRP1 instead. DRP1 is thereby recruited to the MAM, and mitochondrial fission then occurs. Knockdown of FUNDC1, DRP1, or calnexin prevents fission and mitophagy under hypoxic conditions. Thus, FUNDC1 integrates mitochondrial fission and mitophagy at the interface of the MAM by working in concert with DRP1 and calnexin under hypoxic conditions in mammalian cells. © 2016 The Authors Source

Wang H.,The Affiliated Hospital of Guangdong Medical University | Feng X.,The Affiliated Hospital of Guangdong Medical University | Ye S.,The Affiliated Hospital of Guangdong Medical University | Wang J.,The Affiliated Hospital of Guangdong Medical University | And 6 more authors.
Surgical Endoscopy and Other Interventional Techniques | Year: 2015

Background and aim: Laparoscopic-assisted surgery (LAC) is an alternative to open surgery for gastrointestinal stromal tumors (GISTs). Endoscopic full-thickness resection (EFTR), a recently developed procedure, is increasingly used to resect GISTs originated from the muscularis propria. In this retrospective study, we aimed to compare EFTR with LAC as minimally invasive treatments for GISTs, especially those with a diameter <2 cm, originating from the muscularis propria. Moreover, we evaluated the clinical efficacy, safety, and feasibility of EFTR for GISTs. Methods: The study included 68 patients with GISTs originating from the muscularis propria (35 patients who underwent EFTR, and 33 who underwent LAC) who were treated at the Affiliated Hospital of Guangdong Medical University (Zhanjiang, China) between January 2011 and December 2013. The therapeutic outcomes of EFTR and LAC were reviewed retrospectively. Results: In the EFTR group, the mean tumor size was 13 ± 5 mm, the mean procedure time was 91 ± 63 min, and the complete resection rate was 100 %. There were 35 “artificial” perforations and four cases of intraoperative bleeding; all complications were successfully managed endoscopically without emergency surgery. In the LAC group, the mean tumor size was 16 ± 4 mm, the mean operation time was 155 ± 37 min, and complications included three wound infections and one anastomotic leakage. Conclusions: EFTR was associated with a lower complication rate than LAC, with favorable en bloc and sufficient tumor tissue for histological diagnosis. EFTR seems to be an efficacious, relatively safe, and minimally invasive treatment for GISTs and could replace LAC surgical resection in cases where the tumor is smaller than 2 cm in diameter. © 2015 Springer Science+Business Media New York Source

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