科创中国

Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is a newly identified anti-apoptotic molecule. Our previous studies have demonstrated that CIAPIN1 is ubiquitously expressed in normal fetal and adult human tissues and confers multidrug resistance in gastric cancer cells, possibly by upregulating the expression of multidrug resistance gene 1 and multidrug resistance-related protein 1. However, fundamental biological functions of CIAPIN1 have not been elucidated. In this study, we first predicted the subcellular localization of CIAPIN1 with bioinformatic approaches and then characterized the intracellular localization of CIAPIN1 in both human and mouse cells by a combination of techniques including (a) immunohistochemistry and immunofluorescence, (b) His-tagged CIAPIN1 expression, and (c) subcellular fractionation and analysisof CIAPIN1 in the fractions by Western blotting. All methods produced consistent results; CIAPIN1 was localized in both the cytoplasm and the nucleus and was accumulated in the nucleolus. Bioinformatic prediction disclosed a putative nuclear localization signal and a putative nuclear export signal within both human and mouse CIAPIN1. These findings suggest that CIAPIN1 may undergo a cytoplasm-nucleus-nucleolus translocation.

Zhiming Hao;Xiaohua Li;Taidong Qiao;Rui Du;Guoyun Zhang;代明 樊

Journal of Histochemistry and Cytochemistry

2006-12

Background: MG7-Ag is a kind of gastric cancer-specific tumor-associated antigen and has been investigated to serve as a marker of gastric cancer for early diagnosis. Methods: Surface plasmon resonance (SPR) sensor was used for the detection of MG7-Ag in the sera of gastric cancer patients to develop an innovative, simple and rapid assay method for early diagnosis. The specific monoclonal MG7 antibodies were used as capture and detection receptors which were immobilized on the surface of SPR sensor chips for MG7-Ag identification in the human sera. The measurements include 9 cases of gastric cancer patients and 2 cases of healthy blood donors and a MKN45 cancer cell lysate solution sample for positive control. Results: The binding of MG7-Ag onto the sensor surface was observed from SPR spectra. The sera of most gastric cancer patients revealed much higher expression level of MG7-Ag than healthy human sera did in SPR measurement. Conclusion: The initial results demonstrate that the SPR biosensor has the potential for its application in the early diagnosis of gastric cancer. However, more tests need to be done to confirm the detection limitation and the criterion for cancer risk evaluation in early diagnosis.

Xiangyi Fang;Jun Tie;Yonghong Xie;Quanjiang Li;Qingchuan Zhao;代明 樊

Cancer Epidemiology

2010-10

Background: Routine examinations have a low specificity and a low positive rate for the diagnosis of peritoneal lesions. This study aimed to evaluate the diagnostic value and safety of ultrasound-guided percutaneous peritoneal lesion biopsies in patients with ascites and/or abdominal distension with unclear causes.Methods: A retrospective analysis was performed in 153 consecutive patients with ascites and/or abdominal distension with unclear causes. All of the patients showed abnormalities of the peritoneum or greater omentum after ultrasonography, and underwent ultrasound-guided percutaneous biopsies using a Bard auto-biopsy gun with 18- or 16-gauge biopsy needles.Results: The success rate of the procedures was 100% (153/153) and the satisfaction rate of the tissue specimens in the biopsy was 91.5% (140/153). A specific histopathological diagnosis was made in 142 out of 153 patients, with an overall diagnostic accuracy of 92.8%. Among the diagnosed patients, 62 were peritoneal metastatic adenocarcinoma, 49 were peritoneal tuberculosis, 11 were peritoneal malignant mesothelioma, 8 were chronic peritoneal infections, 7 were pseudomyxoma peritonei, and 5 were primary peritoneal lymphoma. Only 11 patients did not get a pathologic diagnosis due to the lack of sufficient tissue specimen. No serious complications occurred.Conclusions: Ultrasound-guided percutaneous biopsy could be a simple, safe and accurate diagnostic method in patients with ascites and/or abdominal distension with unclear causes.

Jianhong Wang;Liucun Gao;Shanhong Tang;Tao Li;Yiming Lei;Huahong Xie;Jie Liang;Baojun Chen;Xian Wang;代明 樊

World Journal of Surgical Oncology

2013-10-2

Purpose: Yes-associated protein 1 (YAP1) is a multifunctional protein that can interact with different transcription factors to activate gene expression. The role of YAP1 in tumorigenesis is unclear. We aimed to investigate the functional role of YAP1 in tumorigenesis of gastric cancer. Experimental Design: YAP1 expresson in gastric adenocarcinoma was evaluated. The biological function was determined by proliferation assay, colony formation, cell invasion, and flow cytometric analysis through knocking down or ectopic expressing YAP1 in gastric cancer cell lines coupled with in vivo study. The possible downstream effectors of YAP1 were investigated by expression microarray. Results: YAP1 protein expression was upregulated in gastric cancer. Nuclear accumulation of YAP1 was associated with poor disease-specific survival (P = 0.021), especially in patients with early-stage diseases (P < 0.001). Knockdown YAP1 resulted in a significant reduction in proliferation, anchoragedependent colony formation, cell invasion, and cell motility. Ectopic YAP1 expression promoted anchorage-independent colony formation, induced a more invasive phenotype, and accelerated cell growth both in vitro and in vivo. Microarray analysis highlighted the alteration of MAPK (mitogenactivated protein kinase) pathway by YAP1. We confirmed a constitutive activation of RAF/MEK/ERK (extracellular signal-regulated kinase) in YAP1-expressing MKN45 cells and further showed that YAP1 enhanced serum/epidermal growth factor-induced c-Fos expression in gastric cancer cells. Conclusions: Our findings supported that YAP1 exhibits oncogenic property in gastric cancer. We provided the first evidence that YAP1 exerted the oncogenic function by enhancing the capacity to activate the early-response gene pathway. YAP1 could be a prognostic biomarker and potential therapeutic target for gastric cancer.

Wei Kang;Joanna H.M. Tong;Anthony W.H. Chan;Tin Lap Lee;Raymond W.M. Lung;Patrick P.S. Leung;Ken K.Y. So;Kaichun Wu;代明 樊;Jun Yu;Joseph J.Y. Sung;Ka Fai To

Clinical Cancer Research

2011-4-15

Colon carcinogenesis represents a stepwise progression from benign polyps to invasive adenocarcinomas and distant metastasis. It is believed that these pathologic changes are contributed by aberrant activation or inactivation of protein-coding proto-onco genes and tumor suppressor genes. However, recent discoveries in microRNA (miRNA) research have reshaped our understanding of the role of non-protein-coding genes in carcinogenesis. In this regard, a remarkable number of miRNAs exhibit differential expression in colon cancer tissues. These miRNAs alter cell proliferation, apoptosis and metastasis through their interactions with intracellular signaling networks. From a clinical perspective, polymorphisms within miRNA-binding sites are associated with the risk for colon cancer, whereas miRNAs isolated from feces or blood may serve as biomarkers for early diagnosis. Altered expression of miRNA or polymorphisms in miRNA-related genes have also been shown to correlate with patient survival or treatment outcome. With further insights into miRNA dysregulation in colon cancer and the advancement of RNA delivery technology, it is anticipated that novel miRNA-based therapeutics will emerge.

William K.K. Wu;Priscilla T.Y. Law;Chung W. Lee;Chi H. Cho;代明 樊;Kaichun Wu;Jun Yu;Joseph J.Y. Sung

Carcinogenesis

2011

Background: Air cholangiogram has been used in patients with malignant hilar obstruction to reduce cholangitis after endoscopic retrograde cholangiopancreatography (ERCP). However, it still remains unclear whether CO2 could be used as an alternative for air cholangiography in such patients. Objective: To investigate the effect of CO2 cholangiogram on post-ERCP complications. Design: Prospective, randomized controlled study. Setting: Tertiary care referral center. Patients: 36 patients with Bismuth type II, III or IV were randomized into CO2 group or iodine contrast group (control group). Intervention: Cholangiography was performed by injection of either CO2 or iodine contrast through a sphincterotome. One or two metal stents were placed. Main outcome measures: Post-ERCP complications, length of hospital stay after ERCP, 1-month and 1-year mortality. Result: There was no significant difference in age, gender, symptoms, liver function tests, type of tumor origin and Bismuth type between patients in CO2 and contrast groups (p > 0.05). Compared with one-stent placement, more volume of CO2 and longer operation time were observed when performing two-stent placement (both p < 0.05). The rate of cholangitis in CO2 group was significantly lower than that in control group (5.6% vs. 33.3%, p = 0.04). After ERCP, mean hospital stay time was shorter in CO2 group compared with control (p < 0.05). The difference of 1-month and 1-year mortality between two groups was not significant (both p > 0.05). Conclusion: CO2 cholangiogram could be a safe method to visualize intrahepatic bile duct with low incidence of post-ERCP cholangitis, which could be considered for the patients with malignant hilar obstruction.

Rongchun Zhang;Lina Zhao;Zhiguo Liu;Biaoluo Wang;Na Hui;Xiangping Wang;Rui Huang;Hui Luo;代明 樊;Yanglin Pan;Xuegang Guo

Scandinavian Journal of Gastroenterology

2013-6

OBJECTIVE: To investigate the expression of telomere restriction fragments (TRF) and telomerase activity in human primary gastric carcinoma tissues and their role in tumor transformation and progression. METHODS: The lengths of TRF and activity of telomerase were observed in 17 early gastric carcinoma tissues and 89 advanced gastric carcinoma tissues, using hybridization of nucleic acids directly in agarose gels and telomere repeat amplification protocol (TRAP) assays, corresponding normal gastric mucosa were used as controls. RESULTS: The TRF lengths and telomerase activity in gastric cancer tissues were significantly shorter or higher than those in non-tumor mucosa, and the expression of telomerase activity in abnormal TRF tumor tissues was significantly higher than that in normal TRF tumour tissues. Alterations of TRF and telomerase activity in advanced tumour tissues were higher than those in early tumor tissues. Moreover, significant differences in TRF length were observed between well differentiated and poorly differentiated adenocarcinomas. CONCLUSION: Abnormal TRF status and telomerase reactivation may correlate well with malignant progression of gastric cancer. Telomerase activity and TRF lengths may thus serve as an important additional marker for tumor diagnosis.

F. Zhang;X. Zhang;代明 樊

Chinese Journal of Pathology

1998-12

Y. Pan;L. Zhao;Z. Liu;R. Zhang;N. Hui;代明 樊;X. Guo

Endoscopy

2011

Background: Osteopontin (OPN) was shown to play an important role in the pathogenesis of various inflammatory and fibrotic processes and elevated in fibrotic liver of mouse model. However, the significance of OPN in hepatitis B virus (HBV)-induced liver cirrhosis (LC) remains unclear and is therefore evaluated in this study. Methods: Thirty-nine patients with HBV-induced LC, 30 patients with HBV infection but without cirrhosis, 11 patients with HBV-related hepatocellular carcinoma (HCC) and 14 additional healthy controls were enrolled in this study. Plasma levels of OPN were measured with enzyme-linked immunosorbent assay and the relationship between OPN and clinical parameters was evaluated. Results: When compared to HBV infection group (median 2.16 ng/ml), plasma levels of OPN were significantly increased in cirrhosis (4.52 ng/ml, p < 0.001) and cancer group (13.38 ng/ml, p < 0.001). The OPN level was correlated with the severity of liver damage according to Child-Pugh classification (p = 0.003). It showed at least comparable sensitivity and specificity to predict cirrhosis as aspartate aminotransferase to platelet ratio index, a previously established non-invasive serum marker of cirrhosis. Conclusions: These data suggest that OPN could be used to evaluate the existence of LC, as OPN has previously been reported to be increased in the HCC; this unique feature makes OPN a promising candidate for prediction biomarker in the long-time surveillance of patients with HBV infection to evaluate the risk of cirrhosis and cancer.

L. Zhao;T. Li;Y. Wang;Y. Pan;H. Ning;X. Hui;H. Xie;J. Wang;Y. Han;Z. Liu;代明 樊

International Journal of Clinical Practice

2008-7

OBJECTIVE: To investigate the significance of DARPP-32 protein expression in gastric carcinoma tissue and cell lines. METHODS: The expression of DARPP-32 protein in normal gastric mucosa and gastric carcinoma tissue was evaluated by immunohistochemical staining using streptavidin-biotin complex technique. The expression in gastric carcinoma tissue and cell lines was evaluated by Western blotting. RESULTS: The expression rate of DARPP-32 protein in gastric adenocarcinoma tissue (92.7%) was significantly higher than that in normal gastric mucosa (52.6%, P < 0.05). There was no significant association between DARPP-32 protein expression and degree of tumor differentiation, local invasion and distant metastasis. As compared with adjacent non-carcinomatous gastric mucosa, both DARPP-32 and its truncated isoform t-DARPP were overexpressed in gastric adenocarcinoma tissue (t = 2.45, P = 0.015); and t-DARPP overexpression was more frequently seen. Expression of DARPP-32 and t-DARPP could also be detected in human gastric cancer cell lines. The expression of DARPP-32 protein was obviously reduced in SGC7901 drug-resistant cell strains. CONCLUSIONS: DARPP-32 is overexpressed in gastric carcinoma. It may play an important role in gastric carcinogenesis. The underlying signal pathways in neoplastic gastric epithelium may also be related to the multi-drug resistance property of gastric cancer cells.

Jin Wang;Yang lin Pan;N. Liu;Chang cun Guo;Liu Hong;代明 樊

Chinese Journal of Pathology

2004-8