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1.  Role of periostin and its antagonist PNDA-3 in gastric cancer metastasis 
The extracellular matrix component periostin is a secreted protein that functions as both a cell attachment protein and an autocrine or paracrine factor that signals through the cell adhesion molecule integrins αvβ3 and αvβ5. Periostin participates in normal physiological activities such as cardiac development, but is also involved in pathophysiological processes in vascular diseases, wound repair, bone formation, and tumor development. It is of increasing interest in tumor biology because it is frequently overexpressed in a variety of epithelial carcinomas and is functionally involved in multiple steps of metastasis progression. These include the maintenance of stemness, niche formation, EMT, the survival of tumor cells, and angiogenesis, all of which are indispensable for gastric cancer metastasis. Periostin has been reported to activate the PI-3K/AKT, Wnt, and FAK-mediated signaling pathways to promote metastasis. Therefore, periostin represents a potentially promising candidate for the inhibition of metastasis. In this review article, we summarize recent advances in knowledge concerning periostin, its antagonist PNDA-3, and their influence on such key processes in cancer metastasis as maintenance of stemness, niche formation, epithelial-to-mesenchymal transition, tumor cell survival, and angiogenesis. In particular, we focus our attention on the role of periostin in gastric cancer metastasis, speculate as to the usefulness of periostin as a therapeutic and diagnostic target for gastric cancer metastasis, and consider potential avenues for future research.
PMCID: PMC4351209  PMID: 25759527
Periostin; Cancer; Tumorigenesis; Extracellular matrix; Epithelial-to-mesenchymal transition; Metastasis; Aptamer; PNDA-3
2.  Effect of gastrectomy with bursectomy on prognosis of gastric cancer: A meta-analysis 
World Journal of Gastroenterology : WJG  2014;20(40):14986-14991.
AIM: To evaluate the effect of bursectomy on overall survival, recurrence-free survival and safety of patients with gastric cancer by performing a meta-analysis.
METHODS: A literature search was performed in PubMed, EMBASE, and the Cochrane Library databases for clinical research that compared bursectomy with non-bursectomy published before October 2013. Inclusion and exclusion criteria were established and applied. Overall survival, recurrence-free survival, complications, hospital stay, operative time and blood loss were compared using hazard ratios (HRs), relative risks and weighted mean differences. Stata 12.0 software was used for statistical analysis.
RESULTS: Four studies including 1130 patients were available for the analysis (430 in the bursectomy group, 700 in the non-bursectomy group). No statistically significant difference was observed in the rate of complications between the bursectomy group and the non-bursectomy group. Bursectomy did not have a significant effect (combined HR = 1.14, 95%CI: 0.88-1.47) on overall survival, and it was not a significant factor for recurrence-free survival (combined HR = 1.06, 95%CI: 0.82-1.37).
CONCLUSION: Gastrectomy with bursectomy is not superior to non-bursectomy in terms of survival. Bursectomy is not recommended as a routine procedure for the surgical treatment of gastric cancer.
PMCID: PMC4209563  PMID: 25356060
Gastric cancer; Bursectomy; Prognosis; Gastrectomy; Meta-analysis
3.  Clinicopathological significance and prognostic value of LRP16 expression in colorectal carcinoma 
AIM: To explore the expression of leukemia related protein 16 (LRP16) in colorectal carcinoma, and analyze its correlation with clinicopathologic features and prognosis.
METHODS: Immunohistochemistry for LRP16 was performed in 201 cases of colorectal carcinoma and 60 cases of distal normal mucosa. Medical records were reviewed and clinicopathological analysis was performed.
RESULTS: LRP16 expression was detected in 117 of 201 cases of the colorectal carcinoma and in 21 cases of 60 distal normal mucosa. The expression of LRP16 in carcinoma was significantly higher than that in normal mucosa (χ2 = 9.999, P = 0.002). LRP16 protein expression was found in 43.3% (52/120) of carcinoma at stage I and II, and 80.2% (65/81) of carcinoma at stage III and IV (χ2 =27.088, P = 0.001). Correlation between LRP16 expression and clinicopathological factors was significant in differentiation (P = 0.010), tumor size (P = 0.001), infiltrative depth (P = 0.000) and distant metastasis (P = 0.027). The difference of median survival time between cancer patients with LRP16 expression (38.0 mo) and those without was statistically significant (105.0 mo, Log rank = 41.455, P = 0.001). The multivariate survival analysis revealed that LRP16 expression was correlated significantly (Cox’s regression: P = 0.001, relative risk = 2.082) with shortened survival in the patients with colorectal cancer.
CONCLUSION: The expression of LRP16 is related to the degree of differentiation, invasiveness, metastasis and prognosis of colorectal carcinoma.
PMCID: PMC2848373  PMID: 20355243
Colorectal neoplasms; Immunohistochemistry; Leukemia related protein 16; Prognosis; Clinicopathology
4.  Prognostic role of miR-200c in various malignancies: a systematic review and meta-analysis 
MiR-200c expression is dysregulated in various malignancies and may predict the survival of patients with cancer, although the results of different studies conflict. Therefore, we conducted a meta-analysis to resolve this discrepancy. We queried the PubMed and Embase using multiple search strategies. Data were extracted from studies comparing overall survival and progression-free survival in patients with cancer with high and low levels of miR-200c expression. Fixed and random models were used where appropriate. A combined hazards ratio (HR) was calculated to estimate the association of high levels of miR-200c with survival. We selected 16 studies of 1485 participants for our final meta-analysis. Upregulated expression of miR-200c predicted significantly worse overall survival in patients with cancer (HR 1.51; 95% confidence interval [CI] 1.06-2.16, P = 0.023). Subgroup analysis indicated that high levels of miR-200c was associated with decreased survival of Caucasians and patients with gynecological tumors with pooled HR values of 1.82 (95% CI 1.27-2.26, P = 0.01) and 3.23 (95% CI 1.11-9.38, P = 0.032), respectively. Because of the absence of apparent heterogeneity, the combined HRs were 1.69 (95% CI 1.24-2.30, P = 0.001) for squamous cell carcinoma and 1.91 (95% CI 1.40-2.59, P < 0.001) for samples from peripheral blood. Increased expression of miR-200c significantly associated with shorter progression-free survival of patients with cancer (HR 2.37; 95% CI 1.47-3.81, P < 0.001). Our meta-analysis indicates that the level of miR-200c expression predicted survival of patients with cancer, particularly for Caucasians and patients with gynecological cancer. Increased expression of miR-200c predicted shorter survival of patients with squamous cell carcinomas. Our findings indicate that monitoring the levels of miR-200c in blood may be useful for following tumor progression as well as patients’ prognosis.
PMCID: PMC4402769  PMID: 25932122
Prognosis; miR-200c; cancers; survival; meta-analysis
5.  Hemolysis-free plasma miR-214 as novel biomarker of gastric cancer and is correlated with distant metastasis 
Circulating miRNAs gains popularity for its potential ability to serve as biomarkers of cancer. The aim of present study was to evaluate the usefulness of plasma miR-214 as novel biomarkers for gastric cancer (GC) detection. Attempts were made to address several pitfalls in sample processing and study design in previous studies. We conducted a two-step analysis: (1) in pilot study comprising of 30 patients and 30 controls, levels of miR-214 were significantly higher in primary GC tissues than normal tissues (P = 0.0215). Plasma miR-214 was significantly higher in patients with GC than in controls (P < 0.0001). (2) In test of larger cohort, there was significantly decreasing tendency of plasma miR-214 from patients before, 14 days and 1 month after surgical resection (P < 0.0001). There were significantly higher levels of miR-214 in 80 GC patients than in 70 controls (P < 0.0001). Receiver operating characteristics (ROC) curves yielded area under the curve (AUC) value of 0.845. Moreover, high plasma miR-214 had significant correlation with distant metastasis (P = 0.038). Thus, our data suggest that plasma miR-214 was novel hemolysis-free markers of gastric cancer.
PMCID: PMC4396053  PMID: 25973319
Plasma miR-214; gastric cancer; biomarkers; distant metastasis
6.  Eph receptors and ephrins as targets for cancer therapy 
Eph receptor tyrosine kinases and their ephrin ligands are involved in various signalling pathways and mediate critical steps of a wide variety of physiological and pathological processes. Increasing experimental evidence demonstrates that both Eph receptor and ephrin ligands are overexpressed in a number of human tumours, and are associated with tumour growth, invasiveness and metastasis. In this regard, the Eph/ephrin system provides the foundation for potentially exciting new targets for anticancer therapies for Eph-expressing tumours. The purpose of this review is to outline current advances in the role of Eph receptors and ephrin ligands in cancer, and to discuss novel therapeutic approaches of anticancer therapies.
PMCID: PMC4393718  PMID: 22862837
Eph receptor; Ephrin; therapeutic target
7.  Lgr5 is a potential marker of colorectal carcinoma stem cells that correlates with patient survival 
Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5) has recently been identified as an intestinal stem cell marker. In order to determine whether Lgr5 is a potential marker of cancer stem cells, we investigated whether Lgr5 expression correlated with Ki-67 expression and prognosis in colorectal carcinoma.
Lgr5 and Ki-67 expression were evaluated by immunohistochemistry in 192 colorectal carcinoma specimens. Selection of side population (SP) cells was performed by staining with Hoechest 33342, and Lgr5 expression in Colo205 SP cells was then detected by immunofluorescence.
Lgr5 expression was significantly higher in carcinoma than in normal mucosa (P=0.001). Lgr5 was positively correlated with histological grade (P=0.001), depth of invasion (P=0.001), lymph node metastasis (P=0.001), distant metastasis (P=0.004), pTNM stage (P=0.001), and Ki-67 (r=0.446, P=0.001). Multivariate analysis showed that the effect of Lgr5 on survival was independent of Ki-67 (P=0.037). In the in vitro study, Hoechst low-staining cells were counted in 7% of the Colo205 colon cancer cell line population, and Lgr5 expression was strikingly stronger in Hoechst low-staining cells than in high-staining cells (P=0.001).
These findings suggest that Lgr5 may play an important role in the progression and prognosis of colorectal carcinoma, and may be a potential new therapeutic target for the treatment of colorectal cancer patients. It may also be considered as a potential marker for colorectal cancer stem cells (CSCs).
PMCID: PMC3506563  PMID: 23153436
Colorectal cancer; Lgr5; Prognosis; Cancer stem cells

Results 1-7 (7)