Wang R.-Y.,International Co operation Laboratory on Signal Transduction |
Wang R.-Y.,Eastern Hepatobiliary Surgery Hospital |
Chen L.,International Co operation Laboratory on Signal Transduction |
Chen H.-Y.,International Co operation Laboratory on Signal Transduction |
And 23 more authors.
Gastroenterology | Year: 2013
Background & Aims Aberrant expression of MUC15 correlates with development of colorectal adenocarcinoma, and MUC15 has been reported to prevent trophoblast invasion of human placenta. However, little is known about the role of MUC15 in pathogenesis of hepatocellular carcinoma (HCC). Methods We analyzed HCC samples and matched nontumor liver tissues (controls) collected from 313 patients who underwent hepatectomy in Shanghai, China, from January 2006 through September 2009. Levels of messenger RNAs and proteins were determined by immunohistochemical, quantitative reverse transcription polymerase chain reaction, and immunoblot analyses. Statistical analyses were used to associate levels of MUC15 with tumor features and patient outcomes. Results Levels of MUC15 messenger RNA and protein were reduced in a greater percentage of HCC samples than control tissues. Tumors with reduced levels of MUC15 were more likely to have aggressive characteristics (eg, high levels of α-fetoprotein, vascular invasion, lack of encapsulation, and poor differentiation) than those with low levels. Patients whose tumors had reduced levels of MUC15 had shorter overall survival times (24 months vs 46 months for patients with tumors with high levels of MUC15) and time to disease recurrence. Stable expression of MUC15 in HCC cell lines (SMMC-7721 and HCC-LM3) reduced their proliferation and invasive features in vitro, and ability to form metastatic tumors in mice. MUC15 reduced transcription of the matrix metalloproteinases 2 and 7 increased expression of tissue inhibitor of metalloproteinase-2, which required phosphoinositide 3-kinase-v-akt murine thymoma viral oncogene homolog signaling. Physical interaction between MUC15 and epidermal growth factor receptor led to its relocation and degradation within early endosomes and was required for inactivation of phosphoinositide 3-kinase-v-akt murine thymoma viral oncogene homolog signaling. Conclusions Reduced levels of MUC15 in HCCs are associated with shorter survival times of patients and reduced time to disease recurrence. Expression of MUC15 in HCC cells reduces their aggressive behavior in vitro and in mice by inducing dimerization of epidermal growth factor receptor and decreasing phosphoinositide 3-kinase signaling via v-akt murine thymoma viral oncogene homolog. © 2013 by the AGA Institute.
PubMed | Shanghai JiaoTong University, Nantong University, International Medical University, Second Military Medical University and 6 more.
Type: Journal Article | Journal: Cancer letters | Year: 2016
The extremely poor prognosis of patients with symptomatic hepatocellular carcinoma (HCC) diagnosed clinically at advanced stages suggests an urgent need for biomarkers that can be used for prospective surveillance and pre-clinical screening for early presence of pre-malignant lesions and tumors. In a retrospective longitudinal phase 3 biomarker study in seven medical centers of China, time-series and 6 months interval-serum samples were collected from chronic hepatitis B virus infected (CHB) patient cohorts at the pre-malignant or pre-clinical stages (average 6 months prior to clinical diagnosis) and CHB patients that did not develop cancer, and circulating miRNAs measured. A set of serum miRNAs including miR-193a-3p, miR-369-5p, miR-672, miR-429 and let-7i* were identified in pre-clinical HCC patients and have the potential to screen for CHB patients at high risk to develop HCC 6-12 months after miRNAs measurement. These circulating miRNAs combined with the conventional screening tools using -fetoprotein and ultrasound, may have great promise for the prediction and prevention of HCC in high-risk populations.
Zhang C.,Nanjing University |
Wang C.,Nanjing University |
Chen X.,Nanjing University |
Yang C.,Nanjing University |
And 14 more authors.
Clinical Chemistry | Year: 2010
BACKGROUND: Sensitive and specific biomarkers for the early detection of esophageal squamous cell carcinoma (ESCC) are urgently needed to reduce the high morbidity and mortality of the disease. The discovery of serum microRNAs (miRNAs) and their unique concentration profiles in patients with various diseases makes them attractive, novel noninvasive biomarkers for tumor diagnosis. In this study, we investigated the serum miRNA profile in ESCC patients to develop a novel diagnostic ESCC biomarker. METHODS: Serum samples were taken from 290 ESCC patients and 140 age- and sex-matched controls. Solexa sequencing technology was used for an initial screen of miRNAs in serum samples from 141 patients and 40 controls. A hydrolysis probe - based stem - loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted in the training and verification phases to confirm the concentrations of selected miRNAs in serum samples from 149 patients and 100 controls. RESULTS: The Solexa sequencing results demonstrated marked upregulation of 25 serum miRNAs in ESCC patients compared with controls. RT-qPCR analysis identified a profile of 7 serum miRNAs (miR-10a, miR-22, miR-100, miR-148b, miR-223, miR-133a, and miR-127-3p) as ESCC biomarkers. The area under the ROC curve for the selected miRNAs ranged from 0.817 to 0.949, significantly higher than for carcinoembryonic antigen (0.549; P < 0.0005). More importantly, this panel of 7 miRNAs clearly distinguished stage I/II ESCC patients from controls. CONCLUSIONS: This panel of 7 serum miRNAs holds promise as a novel blood-based biomarker for the diagnosis of ESCC. © 2010 American Association for Clinical Chemistry.
Shi Y.,Nanjing Medical University |
Lu J.,Cancer Hospital of Jiangsu Province |
Zhou J.,Taizhou People Hospital |
Tan X.,Nanjing Medical University |
And 5 more authors.
Biochemical and Biophysical Research Communications | Year: 2014
Data derived from massive cloning and traditional sequencing methods have revealed that long non-coding RNAs (lncRNA) play important roles in the development and progression of cancer. Although many studies suggest that the lncRNAs have different cellular functions, many of them are not yet to be identified and characterized for the mechanism of their functions. To address this question, we assay the expression level of lncRNAs-Loc554202 in breast cancer tissues and find that Loc554202 is significantly increased compared with normal control, and associated with advanced pathologic stage and tumor size. Moreover, knockdown of Loc554202 decreased breast cancer cell proliferation, induced apoptosis and inhibits migration/invasion in vitro and impeded tumorigenesis in vivo. These data suggest an important role of Loc554202 in breast tumorigenesis. © 2014 Elsevier Inc. All rights reserved.
Pan X.,Cancer Hospital of Jiangsu Province |
Wang R.,Nanjing University |
Wang Z.-X.,Nanjing Medical University
Molecular Cancer Therapeutics | Year: 2013
MicroRNAs (miRNA) are small noncoding RNAs that converge to maintain an intrinsic balance of various processes, including cell proliferation, differentiation, and apoptosis. Recent research efforts have been devoted to translating these basic discoveries into applications that could improve the early diagnosis and therapeutic outcome of patients with cancer. Early studies have shown that miRNA-451 (miR-451) is widely dysregulated in human cancers and plays a critical role in tumorigenesis and tumor progression. In this review, we summarize the potential use of miR-451 for cancer diagnosis, prognosis, and treatment. In addition, we discuss the possible mechanisms of miR-451 dysregulation and future challenges in development of miR-451 as a noninvasive biomarker and a potential therapeutic target in human cancers. ©2013 AACR.
Zhang L.-Q.,Nanjing Medical University |
Wang J.,Geriatric Institution of Jiangsu Province |
Shang J.-Q.,Cancer Hospital of Jiangsu Province |
Bai J.-L.,Nanjing Medical University |
And 4 more authors.
International Journal of Colorectal Disease | Year: 2011
Purpose Studies investigating the association between genetic polymorphism of cyclin D1 (CCND1) G870A and risk of colorectal cancer (CRC) reported conflicting results. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Materials and methods We performed an extensive search of relevant studies and carried out a meta-analysis, including 20 studies with 5,975 cases and 8,333 controls, to obtain a more precise estimate. Results Overall, significantly elevated colorectal cancer risk was associated with variant allele 870A when all studies were pooled (AA vs. GG: OR=1.23, 95% CI=1.04- 1.44; GA vs. GG: OR=1.13, 95% CI=1.01-1.26; dominant model: OR=1.16, 95% CI=1.03-1.31). In the subgroup analysis by ethnicity, significantly increased risks were detected among Caucasians (AA vs. GG: OR=1.27, 95% CI=1.04-1.44; dominant model: OR=1.17, 95% CI=1.02- 1.34).We also observed sporadic CRC with an increased cancer susceptibility (AA vs. GG: OR=1.24, 95% CI=1.04- 1.48; dominant model: OR=1.17, 95% CI=1.04-1.33), when colorectal cancer was stratified into sporadic CRC and hereditary nonpolyposis colorectal cancer (HNPCC). However, no significant associations were found in both Asians and HNPCC patients for all genetic models. Conclusion Result suggests that the cyclin D1 870A allele is a low-penetrant risk factor for developing sporadic colorectal cancer, especially among Caucasians. © Springer-Verlag 2011.
Zhang L.Q.,Nanjing Medical University |
Huang X.-E.,Cancer Hospital of Jiangsu Province |
Wang J.,Geriatric Institution of Jiangsu Province |
Shang J.Q.,Nanjing Medical University |
And 4 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2011
Purpose: Studies of the association between the cyclin D1 (CCND1) G870A genetic polymorphism and risk of colorectal cancer (CRC) have generated conflicting results. In order to derive a more precise estimation, a meta-analysis was here performed. Materials and methods: An extensive search of relevant studies was carried out as a meta-analysis of twenty studies with 5,975 cases and 8,333 controls. Results: Overall, a significantly elevated colorectal cancer risk was associated with variant allele 870A when all studies were pooled (AA vs. GG: OR = 1.23, 95%CI = 1.04-1.44; GA vs. GG: OR = 1.13, 95%CI = 1.01-1.26; dominant model: OR = 1.16, 95%CI = 1.03-1.31). In the subgroup analysis by ethnicity, significantly increased risks were detected among Caucasians (AA vs. GG: OR = 1.27, 95%CI = 1.04-1.44; and dominant model: OR = 1.17, 95%CI = 1.02-1.34). With stratification into sporadic CRC and hereditary nonpolyposis colorectal cancer (HNPCC), the former demonstrated increased cancer susceptibility (AA vs. GG: OR = 1.24, 95%CI = 1.04-1.48; dominant model: OR = 1.17, 95%CI = 1.04-1.33). However, no significant associations were found in either Asians or HNPCC patients for any genetic model. Conclusion: The results suggest that the cyclin D1 870A allele is a low-penetrant risk factor for development of sporadic colorectal cancer, especially among Caucasians.
Yin G.,Cancer Hospital of Jiangsu Province |
Xu Q.,Cancer Hospital of Jiangsu Province |
Chen S.,Cancer Hospital of Jiangsu Province |
Bai X.,Cancer Hospital of Jiangsu Province |
And 4 more authors.
Korean Journal of Radiology | Year: 2012
Objective: To retrospectively evaluate the feasibility and effectiveness of three-tube insertion for the treatment of postoperative gastroesophageal anastomotic leakage (GEAL). Materials and Methods: From January 2007 to January 2011, 28 cases of postoperative GEAL after an esophagectomy with intrathoracic esophagogastric anastomotic procedures for esophageal and cardiac carcinoma were treated by the insertion of three tubes under fluoroscopic guidance. The three tubes consisted of a drainage tube through the leak, a nasogastric decompression tube, and a nasojejunum feeding tube. The study population consisted of 28 patients (18 males, 10 females) ranging in their ages from 36 to 72 years (mean: 59 years). We evaluated the feasibility of three-tube insertion to facilitate leakage site closure, and the patients' nutritional benefit by checking their serum albumin levels between pre- and post-enteral feeding via the feeding tube. Results: The three tubes were successfully placed under fluoroscopic guidance in all twenty-eight patients (100%). The procedure times for the three tube insertion ranged from 30 to 70 minutes (mean time: 45 minutes). In 27 of 28 patients (96%), leakage site closure after three-tube insertion was achieved, while it was not attained in one patient who received stent implantation as a substitute. All patients showed good tolerance of the three-tube insertion in the nasal cavity. The mean time needed for leakage treatment was 21 ± 3.5 days. The serum albumin level change was significant, increasing from pre-enteral feeding (2.5 ± 0.40 g/dL) to post-enteral feeding (3.7 ± 0.51 g/dL) via the feeding tube (p < 0.001). The duration of follow-up ranged from 7 to 60 months (mean: 28 months). Conclusion: Based on the results of this study, the insertion of three tubes under fluoroscopic guidance is safe, and also provides effective relief from postesophagectomy GEAL. Moreover, our findings suggest that three-tube insertion may be used as the primary procedure to treat postoperative GEAL.
Li G.,81th Hospital of PLA |
Hou N.,Cancer Hospital of Jiangsu Province
Chinese Journal of Pathology | Year: 2014
Objective To investigate the frequency of anaplastic lymphoma kinase (ALK) expression in non-small cell lung cancer (NSCLC) patients and its correlation with the clinicopathologic features. Methods ALK immunohistochemistry and ALK fluorescent in situ hybridization (FISH) were performed on formalin-fixed, paraffin-embedded tissue in 100 cases of NSCLCs between 2011 and 2013. Relevant clinicopathologic data were collected and correlated with ALK expression. Results All patients with immunohistochemical score of 3 (n=12) were FISH-positive and all patients with score ofO (n=78) were FISH-negative. Among patients with immunohistochemical scores of 1 and 2, 2/3 and 6/7 were FISH-positive, respectively. The sensitivity and specificity of ALK immunohistochemistry with intensity score of 1 or more were 100% and 98%, respectively. Invasive mucinous adenocarcinoma, solid or acinar growth pattern, presence of mucous cells (signet-ring cells or goblet cells), extracellular mucus and lack of significant nuclear pleomorphism characterized ALK-rearranged cancer. Conclusions ALK-rearranged cancers possess specific histological features. Immunohistochemistry can be used as a routine test for screening ALK-positive cases in advanced NSCLC, and FISH testing should be used to confirm ALK translocation for patients with tumors showing staining for ALK by immunohistochemistry. All of these can help physicians identify patients who may benefit from targeted therapy.
Jiang F.,Cancer Hospital of Jiangsu Province |
Yu M.F.,Cancer Hospital of Jiangsu Province |
Ren B.H.,Cancer Hospital of Jiangsu Province |
Yin G.W.,Cancer Hospital of Jiangsu Province |
And 2 more authors.
Journal of Surgical Research | Year: 2011
Objective: We seek to retrospectively analyze the nasogastric placement of sump tube through the leak for the treatment of intra-thoracic esophagastric anastomotic leak after esophagectomy for esophageal carcinoma. Materials and Methods: Esophagectomy with intrathoracic esophagogastric anastomotic procedures were performed in 2954 patients who suffered from esophageal carcinoma in our hospital between May 2004 and July 2008. Anastomotic leak had developed in 38 patients, of whom four patients were treated by reoperations. Stent insertion, the traditional "three-tube method" and the nasogastric placement of sump tube through the leak were applied in two, seven, and 25 patients, respectively. Results: The presence of anastomotic leak was proven by radiographic contrast examinations in 38 patients (1.3%). Among them, four received reoperations and recovered. Two patients were treated with the placement of self-expanding metallic coated stents and both died 10 and 13 d after placement due to uncontrollable hematemesis. Seven and 25 patients were managed by the traditional "three-tube method" and the nasogastric placement of sump tube through the leak, respectively. The mean time interval of the leak treatment was 42 d in the traditional "three-tube method" group and 31.2 d in the nasogastric placement of sump tube through the leak group, and the relatively average hospital mortality rates were 14.3% and 12%, respectively. Conclusion: The nasogastric placement of sump tube through the leak appears to be an effective, technically feasible, and minimally invasive option for the treatment of intrathoracic esophagogastric anastomotic leak. © 2011 Elsevier Inc. All rights reserved.