Qingdao, China
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Shen E.,First Peoples Hospital of Yueyang | Liu C.,Shanghai University | Wei L.,401 Hospital of PLA | Hu J.,First Peoples Hospital of Yueyang | And 3 more authors.
Tumor Biology | Year: 2014

Background: Published data regarding the association between the APE1 Asp148Glu polymorphism and colorectal cancer susceptibility remained controversial. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship. Materials and methods: We systematically searched PubMed, Embase, and Web of Science with a time limit of August 19, 2013. Summary odds ratios (ORs) with 95 % CIs were used to assess the strength of association between the APE1 Asp148Glu polymorphism and colorectal cancer susceptibility using random-effects model. Results: A total of eight case-control studies including 2,597 cases and 3,063 controls were included for analysis. Overall, no significant associations were found between the APE1 Asp148Glu polymorphism and colorectal cancer susceptibility for GG vs TT (OR = 1.00, 95 % CI = 0.73-1.36, p = 0.00 for heterogeneity), TG vs TT (OR = 1.17, 95 % CI = 0.88-1.55, p = 0.00 for heterogeneity), the dominant model GG + TG vs TT (OR = 1.21, 95 % CI = 0.91-1.60, p = 0.00 for heterogeneity) nor the recessive model GG vs TG + TT(OR = 0.95, 95 % CI = 0.75-1.20, p = 0.02 for heterogeneity). In subgroup analysis, no significant associations were found in the Asian or Caucasian populations. Conclusion: This meta-analysis suggested that the APE1 Asp148Glu polymorphism was not associated with colorectal cancer susceptibility among Asians or Caucasians. © 2013 International Society of Oncology and BioMarkers (ISOBM).

Gao Y.,Changzheng Hospital | Gao Y.,401 Hospital of PLA | Chen Y.,Changhai Hospital | Xu D.,Changzheng Hospital | And 3 more authors.
BMC Cancer | Year: 2014

Background: Annexin-1 contributes to the pathological consequence and sequelae of most serious human diseases including cardiovascular disease and cancer. Although diverse roles in carcinogenesis have been postulated, its role in human gastrointestinal cancers still remains controversial.Methods: The mRNA and protein expression profiles of ANXA1 were studied in human esophageal, gastric, pancreatic, colorectal, liver, and bile duct cancers using Real-Time PCR, western blotting, and immunohistochemistry. Gain/loss-of-function by pcDNA3.1-ANXA1 and ANXA1-shRNA was performed in gastric cancer cells.Results: ANXA1 was widely expressed in adult gastrointestinal tissue. All methods showed that ANXA1 was down-regulated in esophageal, gastric, and bile duct cancers, but up-regulated in pancreatic cancer. Forced ANXA1 expression in gastric cancer cells leads to cell growth inhibition and concomitantly modulates COX-2 expression. We confirm loss of ANXA1 and overexpression of COX-2 in clinical gastric cancer, suggesting that the anti-proliferative function of ANXA1 against COX-2 production might be lost.Conclusions: ANXA1 expression is " tumor-specific" and might play a multifaceted role in cancer development and progression. ANXA1 was widely expressed in normal gastrointestinal epithelium, suggesting its role in the maintenance of cellular boundaries. Furthermore, ANXA1 regulates GC cell viability via the COX-2 pathway. © 2014 Gao et al.; licensee BioMed Central Ltd.

Yang S.-Z.,401 Hospital of PLA | Zhang W.,401 Hospital of PLA | Yuan W.-S.,401 Hospital of PLA | Dong J.-H.,Tsinghua University
Medicine (United States) | Year: 2015

Hepatocellular carcinoma (HCC) is one of the most malignant cancers and ranks as the third leading cause of cancer-related death in the world. However, some patients with untreated HCC can experience spontaneous regression, a rare phenomenon that has been observed in various malignancies. Here, we report a unique case with untreated HCC, who first underwent a spontaneous cancer regression after the spontaneous clearing of chronic hepatitis B virus (HBV) infection from the liver as evidenced by hepatitis B virus surface antigen (HBsAg) seroconversion; then developed the recurrent HCC with epithelial-mesenchymal transition (EMT) after 14 years. We hypothesized that a strengthened immune system in response to HBV infection may have led to immune-mediated spontaneous cancer regression. The later recurrence of HCC may suggest the host's immune system was no longer able to contain HCC since aging and other chronic diseases may have significantly weakened the immune surveillance. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Yu H.,General Hospital of PLA | Yang J.,General Hospital of PLA | Jiao S.,General Hospital of PLA | Li Y.,General Hospital of PLA | And 2 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2014

Purpose: T-box transcription factor 21 (T-bet) is a key lineage-defining transcription factor. The purpose of this study was to verify the relationship between T-bet expression in primary tumors and prognosis of breast cancer. Methods: T-bet protein expression was immunohistochemically detected on surgically-obtained tumor samples of 130 (stage I-III) invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Results: T-bet was expressed in the nuclei and cytoplasm of both tumor cells and tumor-infiltrating lymphocytes. In LOG-RANK analysis, higher density of interstitial T-bet+ interstitial lymphocytes was related with longer distant disease-free survival (DDFS) (P = 0.047); higher tumor nuclei T-bet expression was related with shorter DFS (P = 0.021) and DDFS (P = 0.026). Cox multivariate analysis showed that density of interstitial T-bet+ interstitial lymphocytes was an independent positive prognostic factor for DFS (HR = 0.474, P = 0.051) and DDFS (HR = 0.414, P = 0.030); tumor nuclei CTLA-4 expression was an independent adverse prognostic factor for DFS (HR = 3.007, P = 0.003), DDFS (HR = 2.931, P = 0.005) and OS (HR = 2.352, P = 0.029). Conclusions: This study found that, high tumor nuclei T-bet expression in primary tumors of breast cancer was correlated with poor prognosis and high density of T-bet+ interstitial lymphocytes in primary tumors of breast cancer were correlated with favorable prognosis.

PubMed | Ocean University of China, 401 Hospital of PLA, Tangdu Hospital and University of Wolverhampton
Type: | Journal: Experimental & molecular medicine | Year: 2016

Renal cell carcinoma (RCC), one of the most common kidney cancers, has a poor prognosis. Epithelial to mesenchymal transition (EMT) is a hallmark of carcinoma invasion and metastasis. Several studies have examined the molecular regulation of EMT, but the relationship between histone demethylases and EMT is little understood. In this study, we investigated the role of retinoblastoma-binding protein-2 (RBP2), a histone demethylase that is highly expressed in RCC and is positively correlated with poor RCC prognosis in the regulation of EMT. We found that ectopic overexpression of RBP2 can induce cancer stem cell-like (CSC) phenotypes through EMT in RCC cells by converting them to a more mesenchymal phenotype. This results in increased resistance to apoptosis, which leads to enhanced tumor growth in xenograft models. Together, our data show that RBP2 is an epigenetic regulator that has an important role in the initiation of CSC phenotypes through EMT, leading to tumor progression. RBP2 is also a novel biomolecule for RCC diagnosis, and prognosis and may be a therapeutic target.

Liu Y.,401 Hospital of PLA | Wu H.,General Hospital of Bei Jing Command of PLA | Zhu Y.,401 Hospital of PLA | Gao Y.,401 Hospital of PLA
International Journal of Clinical and Experimental Medicine | Year: 2015

Objective: Abundance of evidence implicated that leptin may play a decisive role in cancer occurrence, but the reported results varied across the individually published studies. The objective of this study is to access to what extent the extensively studied -2548G/A polymorphism of LEP gene acts on the onset of multiple cancers. Methods: Eligible studies included in this meta-analysis were identified electronically in PubMed and Embase, and manually in relevant literature. Crude odds ratio (OR) with corresponding 95% confidence interval (CI) was calculated to estimate the risk of cancer associated with the -2548G/A polymorphism. Results: 12 association studies with a total of 5,618 cancer cases and 6,509 healthy controls were pooled into this meta-analysis. The results revealed that compared with the G allele, the A allele was associated with modestly increased risk of overall cancer (OR, 1.21; 95% CI, 1.02-1.44). Following further stratified analyses, a borderline association was indicated in prostate cancer (OR, 1.18; 95% CI, 1.00-1.39), breast cancer (OR, 1.11; 95% CI, 1.00-1.22) and Caucasians (OR, 1.19; 95% CI, 1.00-1.41). Conclusions: This meta-analysis reveals that the A allele of -2548G/A polymorphism may be a determinant of cancer development. © 2014, E-Century Publishing Corporation. All rights reserved.

Zhang W.,401 Hospital of PLA | Yu W.-J.,Qingdao University | Li Y.-J.,Qingdao University
Chinese Journal of Pathology | Year: 2012

Objective To study the clinicopathologic features, immunohistochemical profiles and prognosis of chromophobe renal cell carcinoma (ChRCC). Methods Forty-two cases of ChRCC were retrieved from the archival files of the Affiliated Hospital of Qingdao University, 401 Hospital of PLA and Qingdao Municipal Hospital from 2003 to 2011. The clinical and pathologic features of the tumors were reviewed. Hale colloidal iron staining was performed and EnVision immunohistochemistry was used to detect the expression of a series of immunologic markers. Forty cases of clear cell renal cell carcinoma and 10 cases of renal oncocytoma were selected as controls. Results The patients included 17 males and 25 females. The age of patients ranged from 39 years to 78 years ( median age = 57 years ). On gross examination, the tumors ranged from 2 cm to 19 cm in greatest dimension (mean size =7. 3 cm). Histologically, the tumors were mainly composed of solid sheets, acini or tubules of malignant cells. The tumor cells contained clear finely reticular ("chromophobe") and eosinophilic cytoplasm with perinuclear clearing. The nuclear outline was irregular and wrinkled. Nucleoli were inconspicuous and mitotic figures were barely seen. Hale colloidal iron stain was positive in all cases. Immunohistochemically, the tumor cells were variably positive for EMA (100% ,42/42), CK7 ( 95. 2% ,40/42) , Ksp-cad ( 92. 9% , 39/42 ), CK18 (88. 1% ,37/42), CD117 (61.9,26/42) , CD10 (31. 0% , 13/42) and PAX2 (28. 6% , 12/42). They were negative for vimentin, CA IX and TFE3. The follow-up period in 31 patients ranged from 2 to 77 months (average duration =29 months). Three patients died of tumor metastasis 3,8,13 months respectively after the operation. Twentyeight patients were still alive without evidence of tumor recurrence. Conclusions ChRCC predominantly occurs in middle-aged and elderly patients. It often carries a favorable prognosis. The presence of plant celllike morphology, pale cells with uniform reticular microvesicular appearance and perinuclear clearing are characteristic histologic features. The diffuse positivity for Hale colloidal iron stain and EMA/CK7/Kspcadherin/CD117-positive immunoprofiles are also useful in differential diagnosis.

PubMed | 401 Hospital of PLA and Qingdao University
Type: Journal Article | Journal: Oncology letters | Year: 2016

In order to determine whether microRNA (miR)-300 is a diagnostic and prognostic biomarker in osteosarcoma, the miR-300 levels in serum of 114 osteosarcoma patients and 114 healthy controls were compared, followed by serum analysis of the differences between the pre-operative and post-operative sera of these osteosarcoma patients. It was observed that the concentration levels of miR-300 in the serum of osteosarcoma patients was significantly higher than those in the serum of healthy controls (P<0.01). Furthermore, the concentration levels of miR-300 in the post-operative serum were significantly reduced when compared with the pre-operative serum levels (P<0.001). High miR-300 levels in serum correlated significantly with clinical stage, distant metastasis and poor survival of osteosarcoma patients. Notably, serum miR-300 was an independent prognostic marker for osteosarcoma. In conclusion, our results suggested that serum miR-300 may be a potential and useful noninvasive biomarker for the early detection of osteosarcoma.

PubMed | 401 Hospital of PLA, Chongqing Medical University and Institute & Hospital of Hepatobiliary Surgery
Type: Journal Article | Journal: Surgery | Year: 2015

The boundary of the target hepatic segment within the liver parenchyma cannot be marked by the use of a conventional anatomic hepatectomy approach. This study describes a novel methylene blue staining technique for guiding the anatomic resection of hepatocellular carcinoma (HCC).Between February 2009 and February 2012, anatomic hepatectomy was performed in 106 patients with HCC via a novel, sustained methylene blue staining technique. Sustained staining was achieved by injecting methylene blue into the distal aspect of the portal vein after exposing Glissons sheath. The hepatic pedicle was immediately ligated, and the hepatic parenchymal transection was performed along the interface between methylene blue stained tissue and unstained tissue.Anatomic hepatectomies included subsegmentectomy (n=16), monosegmentectomy (n=57), multisegmentectomy (n=27), and hemihepatectomy (n=6). The portal vein was injected successfully with methylene blue in 100% of cases, and complete staining of the target hepatic segment was achieved in 98 of 106 (92.5%) cases. Mean intraoperative bleeding was 36090mL, and the postoperative complication rate was 24.5% (26/106). No perioperative mortality occurred. Operative margins were all negative on pathologic examination. Mean duration of postoperative follow-up was 40months (range, 24-60). No local recurrence (around the operative margin) occurred.This novel technique of achieving sustained staining by injecting methylene blue then immediately ligating the hepatic pedicle is simple and feasible. It can guide the selection of the operative margin during hepatic parenchyma transection to improve the accuracy of anatomic hepatectomy for the treatment of HCC.

PubMed | 401 Hospital of PLA and Qingdao University
Type: Comparative Study | Journal: Zhonghua bing li xue za zhi = Chinese journal of pathology | Year: 2016

To study the immunohistochemical expression of S100A1, GLUT-1 and Cavolin-1 and its diagnostic significance in renal tumors with oncocytic features.Tissue microarray and immunohistochemical staining for S100A1, GLUT-1 and Cavolin-1 were carried out in 59 cases of renal tumors with oncocytic features, including 19 cases of renal oncocytoma, 15 cases of clear cell renal cell carcinoma (CCRCC) with eosinophilic cells, 11 cases of eosinophilic variant of chromophobe renal cell carcinoma, 7 cases of oncocytic papillary renal cell carcinoma and 7 cases of epithelioid angiomyolipoma.S100A1 was expressed in renal oncocytoma, with a positive propotion of 16/19 (including 14 cases showing widespread and strong positivity). On the other hand, the rate of expression of S100A1 was 2/11 in eosinophilic variant of chromophobe renal cell carcinoma, 10/15 in CCRCC with eosinophilic cells, 3/7 in oncocytic papillary renal cell carcinoma and 6/7 in epithelioid angiomyolipoma (P>0.05). The difference of S100A1 expression between renal oncocytoma and eosinophilic variant of chromophobe renal cell carcinoma was statistically significant. GLUT-1 was located in cell membrane, with a positive rate of 13/15 in CCRCC with eosinophilic cells, 7/19 in renal oncocytoma, 4/7 (weak) in oncocytic papillary renal cell carcinoma, 1/11 in eosinophilic variant of chromophobe renal cell carcinoma and 0/7 in epithelioid angiomyolipoma. The rate of expression of Cav-1 was 6/15 in CCRCC with eosinophilic cells, 2/7 in oncocytic papillary renal cell carcinoma, 5/7 in epithelioid angiomyolipoma, 2/11 (weak) in eosinophilic variant of chromophobe renal cell carcinoma and 0/19 in renal oncocytoma. S100A1 showed high sensitivity and 50% specificity in the diagnosis of renal oncocytoma. GLUT-1 and Cav-1 showed high specificity and sensitivity in the diagnosis of CCRCC and epithelioid angiomyolipoma.S100A1 is widely expressed in various oncocytic renal neoplasms and helpful in differential diagnosis of renal oncocytoma from eosinophilic variant of chromophobe renal cell carcinoma, but not from other 3 oncocytic renal tumors. Overexpression of GLUT-1 can be used in distinction between CCRCC and renal oncocytoma. Cav-1 is widely expressed in CCRCC and epithelioid angiomyolipoma but not in renal oncocytoma. Cav-1 expression thus rules out renal oncocytoma.

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