Publications by authors named "Yunping Zhao"

23 Publications

  • Page 1 of 1

CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis.

Open Med (Wars) 2021 4;16(1):104-116. Epub 2021 Jan 4.

Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, No 295 Xichang Road, Kunming 650032, Yunnan, China.

Background: The aim of this study was to investigate the circ_0004370 expression in EC, its effects on cell proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) process, and the underlying regulatory mechanisms in EC.

Methods: The protein levels of COL1A1 and EMT-related proteins were detected by western blot. The role of circ_0004370 on cell viability, proliferation, and apoptosis was analyzed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and flow cytometry, respectively. The transwell assay was used to examine cell migration and invasion. The binding sites between miR-1301-3p and circ_0004370 or COL1A1 were predicted by starbase software and confirmed by dual-luciferase reporter assay and RNA pull-down assay.

Results: We discovered that circ_0004370 was remarkably upregulated in EC tissues and cells. Knockdown of circ_0004370 inhibited cell proliferation, migration as well as invasion, and promoted apoptosis , while its effect was rescued by miR-1301-3p inhibition. And circ_0004370 mediated the EMT process in EC cells. Moreover, we explored its regulatory mechanism and found that circ_0004370 directly bound to miR-1301-3p and COL1A1 was verified as a target of miR-1301-3p. COL1A1 was highly expressed in EC cells and upregulation of COL1A1 reversed the effects of miR-1301-3p on cell proliferation, migration, invasion, and apoptosis. In addition, silencing of circ_0004370 reduced tumor volumes and weights . We showed that circ_0004370/miR-1301-3p/COL1A1 axis played the critical role in EC to regulate the cell activities.

Conclusion: Circ_0004370 promotes EC proliferation, migration and invasion, and EMT process and suppresses apoptosis by regulating the miR-1301-3p/COL1A1 axis, indicating that circ_0004370 may be used as a potential therapeutic target for EC.
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http://dx.doi.org/10.1515/med-2021-0001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801883PMC
January 2021

An Accelerator Design Using a MTCA Decomposition Algorithm for CNNs.

Sensors (Basel) 2020 Sep 28;20(19). Epub 2020 Sep 28.

College of Computer, National University of Defense Technology, Changsha 410073, China.

Due to the high throughput and high computing capability of convolutional neural networks (CNNs), researchers are paying increasing attention to the design of CNNs hardware accelerator architecture. Accordingly, in this paper, we propose a block parallel computing algorithm based on the matrix transformation computing algorithm (MTCA) to realize the convolution expansion and resolve the block problem of the intermediate matrix. It enables high parallel implementation on hardware. Moreover, we also provide a specific calculation method for the optimal partition of matrix multiplication to optimize performance. In our evaluation, our proposed method saves more than 60% of hardware storage space compared with the (image to column) approach. More specifically, in the case of large-scale convolutions, it saves nearly 82% of storage space. Under the accelerator architecture framework designed in this paper, we realize the performance of 26.7GFLOPS-33.4GFLOPS (depending on convolution type) on FPGA(Field Programmable Gate Array) by reducing bandwidth and improving data reusability. It is 1.2×-4.0× faster than memory-efficient convolution (MEC) and , respectively, and represents an effective solution for a large-scale convolution accelerator.
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http://dx.doi.org/10.3390/s20195558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583864PMC
September 2020

Effect of polysaccharide extract SPSS1 from Apostichopus japonicas spermary on HepG2 cells via iTRAQ-based proteome analysis.

J Food Biochem 2020 05 11;44(5):e13168. Epub 2020 Mar 11.

Shandong Marine Resource and Environment Research Institute, Yantai, China.

In this study, polysaccharide extract was prepared from Apostichopus japonicus spermary and purified by ion-exchange chromatography and gel filtration chromatography. Two main fractions named SPSS1 and SPSS2 were obtained and analyzed by ultraviolet spectroscopy and mixed with KBr, respectively. Chemical components analysis proved that SPSS1 and SPSS2 were rich in sulfate. Monosaccharide analysis indicated that in addition to the high content of lactose in both kinds of polysaccharides, the highest content of monosaccharide in SPSS1 was galactose, while in SPSS2 it was fucose. Further, the antitumor study of SPSS1 was carried and the results showed that SPSS1 treatment inhibited the proliferation of HepG2 cells. Through the iTRAQ-based proteome analysis, there were 208 differential proteins between control tumor cells and SPSS1 treatment of tumor cells. Compared to control tumor cells, 135 proteins were upregulated and 73 proteins were downregulated in treatment tumor cells. PRACTICAL APPLICATIONS: Our study suggested that polysaccharide from sea cucumbers had the potential to be further developed as antitumor drugs.
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http://dx.doi.org/10.1111/jfbc.13168DOI Listing
May 2020

RNA m A methylation regulates uveal melanoma cell proliferation, migration, and invasion by targeting c-Met.

J Cell Physiol 2020 10 4;235(10):7107-7119. Epub 2020 Feb 4.

School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.

N -methyladenosine (m A) is a novel epitranscriptomic marker that contributes to regulating diverse biological processes through controlling messenger RNA metabolism. However, it is unknown if m A RNA methylation affects uveal melanoma (UM) development. To address this question, we probed its function and molecular mechanism in UM. Initially, we demonstrated that global RNA m A methylation levels were dramatically elevated in both UM cell lines and clinical specimens. Meanwhile, we found that METTL3, a main m A regulatory enzyme, was significantly increased in UM cells and specimens. Subsequently, cycloleucine (Cyc) or METTL3 targeted small interfering RNA was used to block m A methylation in UM cells. We found that Cyc or silencing METTL3 significantly suppressed UM cell proliferation and colony formation through cell cycle G1 arrest, as well as migration and invasion by functional analysis. On the other hand, overexpression of METTL3 had the opposite effects. Furthermore, bioinformatics and methylated RNA immunoprecipitation-quantitative polymerase chain reaction identified c-Met as a direct target of m A methylation in UM cells. In addition, western blot analysis showed that Cyc or knockdown of METTL3 downregulated c-Met, p-Akt, and cell cycle-related protein levels in UM cells. Taken together, our results demonstrate that METTL3-mediated m A RNA methylation modulates UM cell proliferation, migration, and invasion by targeting c-Met. Such a modification acts as a critical oncogenic regulator in UM development.
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http://dx.doi.org/10.1002/jcp.29608DOI Listing
October 2020

miR-142-3p suppresses uveal melanoma by targeting CDC25C, TGFβR1, GNAQ, WASL, and RAC1.

Cancer Manag Res 2019 24;11:4729-4742. Epub 2019 May 24.

School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.

Uveal melanoma (UM) is the most frequent metastatic ocular tumor in adults. Therapeutic intervention remains ineffective since none of the novel procedures used to treat this disease increased survival rates. To deal with this limitation, additional studies are required to clarify its pathogenesis. The current study focused on describing how epigenetic modulation by miR-142-3p affects changes in some cellular functions underlying UM pathogenesis. Microarray analysis identified 374 miRNAs which were differentially expressed between UM cells and uveal melanocytes. miR-142-3p was one of the 10 most downregulated miRNAs. Quantitative RT-PCR analysis confirmed that miR-142-3p expression levels were significantly decreased in both UM cell lines and clinical specimens. The results of the MTS, clone formation, scratch wound, transwell assays, and in vivo biofluorescence imaging showed that miR-142-3p overexpression significantly inhibited cell proliferation, migration, and invasiveness. Nevertheless, miR-142-3p did not affect cell apoptotic activity or sensitivity to doxorubicin. Cell cycle and EdU analysis showed that miR-142-3p overexpression induced G1/G2 cell cycle arrest and reduced DNA synthesis in UM cells. Microarray analysis showed that miR-142-3p mainly regulates the TGFβ signaling pathway, and those in which MAPK and PI3K-Akt are constituents. Functional interactions between miR-142-3p and , , , , and target genes were confirmed based on the results of the luciferase reporter assay and Western blot analysis. CDC25C or RAC1 downregulation is in agreement with cell cycle arrest and DNA synthesis disorder induction, while downregulation of TGFβR1, GNAQ, WASL, or RAC1 accounts for declines in cell migration. miR-143-3p is a potential therapeutic target to treat UM since overriding its declines in expression that occur in this disease reversed the pathogenesis of this disease. Such insight reveals novel biomarker for decreasing UM vitality and for improved tracking of tumor progression.
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http://dx.doi.org/10.2147/CMAR.S206461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541795PMC
May 2019

Up-regulation of CKAP2L expression promotes lung adenocarcinoma invasion and is associated with poor prognosis.

Onco Targets Ther 2019 12;12:1171-1180. Epub 2019 Feb 12.

Department of Cardiovascular and Thoracic, Kunming General Hospital, Kunming, Yunnan 650032, People's Republic of China.

Aim: The purpose of this study is to consider the function of cytoskeleton-associated protein 2-like (CKAP2L) in lung adenocarcinoma (LAD) development and its prognostic value.

Methods: The mRNA expression of CKAP2L and its correlation with clinical factors in LAD patients were analyzed from the data taken from The Cancer Genome Atlas and The First Affiliated Hospital of Kunming Medical University. We constructed H460 and A549 cell lines with silenced CKAP2L using RNA interference. Cell counting kit-8 assay and colony formation assays were carried out to determine the function of CKAP2L in H460 and A549 cell proliferation. Transwell and wound healing assays were applied to determine the effect of CKAP2L on H460 and A549 cell invasion and migration. The influences of CKAP2L on mitogen-activated protein kinase signaling pathway-related proteins were tested by Western blotting.

Results: CKAP2L expression is enhanced in LAD tissues and is predictive of poor prognosis in LAD patients. High expression of CKAP2L is associated with stage (<0.001), lymph node status (=0.002), and metastasis (=0.025). Depletion of CKAP2L dramatically suppressed the proliferation, migration, and invasion of H460 and A549 cells. Moreover, the ratio of p-MEK/ MEK and p-ERK/ERK reduced obviously in A549 cells after depleting CKAP2L.

Conclusion: Our findings implied that CKAP2L might be a promoter of LAD and could serve as a predictor for LAD patients.
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http://dx.doi.org/10.2147/OTT.S182242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388994PMC
February 2019

Inhibition of cell growth and up-regulation of MAD2 in human oesophageal squamous cell carcinoma after treatment with the Src/Abl inhibitor dasatinib.

Clin Sci (Lond) 2012 Jan;122(1):13-24

Thoracic Surgery Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.

Aberrant expression and/or activity of the non-receptor protein tyrosine kinase SFK (Src family kinase) members are commonly observed in progressive stages of human tumours. The aim of the present study was to investigate whether Src is a potential drug target for treating oesophageal squamous cell carcinoma. Compared with the human immortalized oesophageal epithelial cell line SHEE, oesophageal squamous cell carcinoma cells have increased tyrosine phosphorylation activities. We have explored the therapeutic potential of dasatinib, a small-molecule inhibitor that targets multiple cytosolic and membrane-bound tyrosine kinases, for the treatment of oesophageal squamous cell carcinoma. We examined that the effects of dasatinib on proliferation, invasion, apoptosis, spindle checkpoint, cell-cycle arrest and kinase activity in vitro using three human oesophageal carcinoma cell lines KYSE30, KYSE180 and EC109. In nude mouse models, dasatinib treatment effectively inhibited the expression of activated Src, resulting in the inhibition of tumour growth. Multiple drug effect isobologram analysis was used to study interactions with the chemotherapeutic drug docetaxel. As expected, the three oesophageal carcinoma cell lines were highly sensitive to dasatinib, but SHEE cells were not sensitive to this drug. Concentration-dependent anti-proliferative effects of dasatinib were observed in the three oesophageal carcinoma cell lines. Dasatinib significantly inhibited oesophageal carcinoma cell invasion and up-regulation of MAD2 (mitotic arrest-deficient 2), as well as inducing cell apoptosis and cell-cycle arrest. Additive and synergistic interactions were observed for the combination of dasatinib and docetaxel. Therefore it was concluded that dasatinib blocks the G₁/S transition and inhibits cell growth. These results provided a clear biological rationale to test dasatinib as a single agent or in combination with chemotherapy in oesophageal squamous cell carcinoma. Moreover, we have shown in vitro and in vivo that dasatinib might have therapeutic benefit for patients with oesophageal squamous cell carcinoma who are not eligible for surgery.
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http://dx.doi.org/10.1042/CS20110230DOI Listing
January 2012

[Numerical taxonamy of Paris plants].

Zhongguo Zhong Yao Za Zhi 2010 Jun;35(12):1518-20

School of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.

Numerical taxonomic studies were carried out in order to elucidate the taxonomic relationship among 17 species belonging to Paris. Eighteen characters including 10 morphological, 4 pollen morphological, 2 cytotalonomical and 2 habitat characters were used for the analysis. On basis of UPGMA clustering analysis, two subgenus and seven groups were recognized. The classification of the two subgenus was different from the opinion of subgenus Daiswa and subgenus Paris by Li Heng. The classification of sect. Dunnianae, sect. Axiparis and sect. Paris was correspondence with the classification of Li Heng. But sect. Fargesianae, sect. Marmoratae and sect. Thibeticae which were established based on the especially characters by Li Heng were put into cluster 2, cluster 3 and cluster 4.
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http://dx.doi.org/10.4268/cjcmm20101202DOI Listing
June 2010

Decreased expression of CIAPIN1 is correlated with poor prognosis in patients with esophageal squamous cell carcinoma.

Dig Dis Sci 2010 Dec 22;55(12):3408-14. Epub 2010 Apr 22.

State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 710032, Xi'an, Shaanxi Province, People's Republic of China.

Background: CIAPIN1, a newly identified antiapoptotic molecule, is a downstream effector of the receptor tyrosine kinase-Ras signaling pathway in the mouse Ba/F3 pro-B cell line. Neither CIAPIN1 expression nor its clinical significance has been previously examined in esophageal squamous cell carcinoma (ESCC), and the present immunohistochemical analysis is the first study on CIAPIN1 distribution in ESCC.

Aims: To investigate the relationships between the expression of CIAPIN1 and clinicopathological characteristics of ESCC, and evaluate the relationship between the expression of this gene and prognosis in ESCC patients.

Methods: The expression of CIAPIN1 was investigated in 112 surgically resected specimens of ESCC by immunohistochemistry using a specific monoclonal antibody. The relations of CIAPIN1 expression with clinicopathological characteristics and the postoperative survival rate were statistically analyzed.

Results: We found that the expression of CIAPIN1 was statistically correlated with the degree of differentiation, depth of invasion, and lymph node metastasis of ESCC. Consistently, the survival rates of patients with CIAPIN1-negative tumors tended to be statistically lower than those with CIAPIN1-positive tumors. However, no significant difference was observed between CIAPIN1 expression and the patient age, sex, tumor location, and distant metastasis. Furthermore, multivariate analysis was performed by using Cox's proportional hazards model, and the results showed that lymph node metastases and CIAPIN1 expression were two independent prognostic factors.

Conclusions: CIAPIN1 might play an important role in esophageal carcinogenesis, and it could be considered as a valuable prognostic indicator in ESCC. Finally, functional enhancement of CIAPIN1 might lead to a novel strategy for the treatment of SCC in the esophagus.
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http://dx.doi.org/10.1007/s10620-010-1212-7DOI Listing
December 2010

Detection of serum gastric cancer-associated MG7-Ag from gastric cancer patients using a sensitive and convenient ELISA method.

Cancer Invest 2009 Feb;27(2):227-33

State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Shannxi, P.R. China.

Purpose: To seek a high sensitive and convenient method for early diagnosis of gastric cancer by testing MG7-Ag in serum of gastric cancer patients and some other control groups using a convenient ELISA method.

Experiment Design: The expression of serum MG7-Ag was detected in 116 preoperative gastric cancer patients, 63 postoperative gastric cancer patients, 78 precancerous lesion patients, 50 healthy blood donors and patients of other cancers by a convenient ELISA method. For comparison, serum CEA, CA 50, CA 19-9 and TAG-72 were also detected in preoperative gastric cancer patients. Meanwhile, the expression of MG7-Ag was detected by immunohistochemical analysis in the groups of patients with gastric cancer or precancerous lesion mentioned above.

Results: The positive rate of Mg7-Ag determined by ELISA was 83. 6% of preoperative gastric cancer patients, 54.8% of lung cancer patients, 45.5% of rectal cancer patients, 17.6% of colonic cancer patients, 14.2% of breast cancer patients, 47.6% of postoperative gastric cancer patients, 12.8% of precancerous lesions patients and 0% of healthy blood donors, respectively. The sensitivity of ELISA (83.6%) was found to be similar with that of immunohistochemistry (94%, p > 0. 01), while the false positive rate was lower (12.8% vs. 51.3%). MG7-Ag expression level in gastric cancer was correlated with tumor differentiation (p < 0. 01) and pathological stage (p < 0. 01).

Conclusion: This ELISA method may be a non-invasive candidate method for screening of large population with high risk of gastric cancer.
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http://dx.doi.org/10.1080/07357900802175609DOI Listing
February 2009

Expression and prognostic value of ZNRD1 in esophageal squamous cell carcinoma.

Dig Dis Sci 2009 Mar 2;54(3):586-92. Epub 2008 Jul 2.

State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.

The expression of ZNRD1 in esophageal cancer was first investigated by immunohistochemical analysis, RT-PCR and real-time PCR. The ZNRD1 antibody produced a consistently cytoplasmic staining pattern in all epithelial cells. The expression of ZNRD1 was statistically correlated with differentiation, depth of invasion, lymph node metastasis, pathological stage, lymphatic invasion, and vascular invasion. The survival rates of patients with ZNRD1-negative tumors tended to be statistically lower than those with ZNRD1-positive tumors. ZNRD1 expression was also confirmed to be down-regulated in esophageal cancer tissues compared to adjacent non-neoplastic tissues. The results showed that ZNRD1 might play an important role in esophageal carcinogenesis.
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http://dx.doi.org/10.1007/s10620-008-0380-1DOI Listing
March 2009

A new apoptosis inhibitor, CIAPIN1 (cytokine-induced apoptosis inhibitor 1), mediates multidrug resistance in leukemia cells by regulating MDR-1, Bcl-2, and Bax.

Biochem Cell Biol 2007 Dec;85(6):741-50

State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, the Fourth Military Medical University, 17 Changle Western Road, Xi'an 710032, China.

We investigated the role of cytokine-induced apoptosis inhibitor 1 (CIAPIN1), a newly identified apoptosis inhibitor, in leukemia cell multidrug resistance (MDR) and its possible underlying mechanisms. CIAPIN1 was found to be overexpressed at the mRNA and protein levels in the vincristine-induced multidrug-resistant leukemia cell line HL-60/VCR, compared with HL-60, its parental cell line. In this study, we transfected HL-60 with a eukaryotic expression vector of CIAPIN1. In vitro drug sensitivity assays suggested that HL-60-CIAPIN1 cells conferred resistance to both P-glycoprotein (P-gp)-related and -unrelated drugs. Blocking CIAPIN1 expression in HL-60/VCR cells by CIAPIN1-specific small interfering RNA increased the cells' sensitivity to various chemotherapeutic drugs. Flow cytometry results suggested that CIAPIN1 expression could suppress adriamycin-induced apoptosis, accompanied by a decreased accumulation and increased release of adriamycin. Semiquantitative RT-PCR, Western blot analysis, and luciferase reporter assays suggested that CIAPIN1 could significantly upregulate the expression of MDR-1 and Bcl-2, the transcription of the MDR-1 gene, as well as downregulate the expression of Bax. Additionally, the inhibition of CIAPIN1 expression by RNA interference or P-gp inhibitor could partially reverse CIAPIN1-mediated MDR. Taken together, our findings suggest that downregulating CIAPIN1 could sensitize leukemia cells to chemotherapeutic drugs by downregulating MDR-1 and Bcl-2 and by upregulating Bax, yet not altering either glutathione-S-transferase activity or intracellular glutathione content in leukemia cells. Further study of CIAPIN1's function may reveal more of the mechanisms of leukemia MDR and result in the development of strategies to treat leukemia.
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http://dx.doi.org/10.1139/o07-141DOI Listing
December 2007

DARPP-32 mediates multidrug resistance of gastric cancer through regulation of P-gp and ZNRD1.

Cancer Invest 2007 Dec;25(8):699-705

State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.

Here, we firstly investigated the roles of DARPP-32 in multidrug resistance of gastric cancer cells. Inhibition of DARPP-32 by small interfering RNA led to decreased sensitivity of cells to chemotherapeutic drugs, accompanied by increased capacity of cells to efflux adriamycin. Inhibition of DARPP-32 expression could significantly up-regulate the expression of permeability glycoprotein (P-gp) and zinc ribbon domain-containing 1 (ZNRD1), but not alter the expression of multidrug resistance-associated protein or glutathione transferase. The DARPP-32 siRNA-mediated MDR could be reversed by inhibitor of P-gp or siRNA of ZNRD1, indicating DARPP-32 might mediate MDR of gastric cancer through regulation of P-gp and ZNRD1.
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http://dx.doi.org/10.1080/07357900701566304DOI Listing
December 2007

Reversal of migraine symptoms by Helicobacter pylori eradication therapy in patients with hepatitis-B-related liver cirrhosis.

Helicobacter 2007 Aug;12(4):306-8

State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.

Helicobacter pylori infection might be associated with vascular diseases, such as primary Raynaud phenomenon and coronary heart diseases. The possible mechanism might be due to H. pylori antigens causing intermittent vasospasm of arterioles, which also played roles in the development of liver cirrhosis. Migraine, a functional vascular disease, was observed in many patients with cirrhosis in the clinic. This study aimed to assess the effects of H. pylori eradication on migraine symptoms in patients with hepatitis-B-virus-related cirrhosis. The results clearly showed that the intensity, duration, and frequency of attacks of migraine were significantly reduced in all the patients in whom H. pylori has been eradicated. Thus, the study pushed further insight into the mechanisms of migraine pathogenesis.
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http://dx.doi.org/10.1111/j.1523-5378.2007.00512.xDOI Listing
August 2007

Differential expression of calcium-related genes in gastric cancer cells transfected with cellular prion protein.

Biochem Cell Biol 2007 Jun;85(3):375-83

State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.

The prion protein (PrPC) has a primary role in the pathogenesis of transmissible spongiform encephalopathies, which causes prion disorders partially due to Ca2+ dysregulation. In our previous work, we found that overexpressed PrPC in gastric cancer was involved in apoptosis, cell proliferation, and metastasis of gastric cancer. To better understand how PrPC acts in gastric cancer, a human microarray was performed to select differentially regulated genes that correlate with the biological function of PrPC. The microarray data were analyzed and revealed 3798 genes whose expression increased at least 2-fold in gastric cancer cells transfected with PrPC. These genes encode proteins involved in several aspects of cell biology, among which, we specially detected molecules related to calcium, especially the S100 calcium-binding proteins, and found that PrPC upregulates S100A1, S100A6, S100B, and S100P but downregulates CacyBP in gastric cancer cells. We also found that intracellular Ca2+ levels in cells transfected with PrPC increased, whereas these levels decreased in knockdowns of these cells. Taken together, PrPC might increase intracellular Ca2+, partially through calcium-binding proteins, or PrPC might upregulate the expression of S100 proteins, partially through stimulating the intracellular calcium level in gastric cancer. Though the underlying mechanisms need further exploration, this study provides a new insight into the role of PrPC in gastric cancer and enriches our knowledge of prion protein.
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http://dx.doi.org/10.1139/o07-052DOI Listing
June 2007

Expression and prognostic value of MG7-Ag in patients with surgically resectable esophageal squamous cell carcinoma.

Ann Surg Oncol 2007 Sep 15;14(9):2621-7. Epub 2007 Jun 15.

State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, PR China.

Purpose: MG7-Ag is a human gastric-carcinoma-associated antigen. The expression of MG7-Ag was found to increase gradually with the development and progression of gastric cancer. Moreover, a poorer prognosis was found in MG7-Ag positive gastric-carcinoma patients than in MG7-Ag negative patients. However, neither MG7-Ag expression nor its clinical significance has been previously examined in squamous cell carcinoma (SCC) of the esophagus. In this study, we examined the expression of MG7-Ag in esophageal squamous cell carcinomas to assess its value as a prognostic indicator.

Methods: The expression of MG7-Ag was detected in 112 cases of esophageal squamous cell carcinoma (SCC) by immunohistochemical analysis. The relation of MG7-Ag staining with various clinicopathological features was statistically analyzed.

Results: The staining of MG7-Ag was detected in SCC, while not in normal epithelial cells. In esophageal SCC, MG7-Ag was found significantly correlated with depth of invasion (P = .012), in T4, T3 carcinomas but not in T2, T1 carcinomas, lymph node metastases (P = .029), pathological stage (P = .005). Consistently, the survival rate tended to be statistically lower in patients with MG7-Ag positive SCCs than in MG7-Ag negative SCCs (P = .005). However, no significant difference was observed between MG7-expression and patient age, sex, tumor location, differentiation, distant metastasis, and lymphatic invasion.

Conclusion: MG7-Ag might play a positive role in the process of carcinogenesis and progression of esophageal SCC, and it could be considered as one valuable prognostic indicator in esophageal SCC.
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http://dx.doi.org/10.1245/s10434-007-9416-6DOI Listing
September 2007

Reversal of multidrug resistance of adriamycin-resistant gastric adenocarcinoma cells through the up-regulation of DARPP-32.

Dig Dis Sci 2008 Jan 11;53(1):101-7. Epub 2007 May 11.

State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.

We have investigated the roles of dopamine and cAMP-regulated phosphoprotein (DARPP-32) in the multidrug resistance (MDR) of gastric cancer cells and the possible underlying mechanisms. The up-regulation of DARPP-32 was found to significantly enhance the sensitivity of cells of human adriamycin (ADR)-resistant gastric adenocarcinoma cell line SGC7901/ADR to vincristine, ADR, 5-fludrouracil and cisplatin. The results of an in vivo drug sensitivity assay confirmed that DARPP-32 may play a specific role in the MDR of gastric cancer. DARPP-32 significantly down-regulated the expression of P-glycoprotein and zinc ribbon domain-containing 1 (ZNRD1), but did not alter the expression of MDR-associated protein or glutathione-S-transferase. The up-regulation of ZNRD1 significantly inhibited the drug sensitivity of gastric cancer cells over-expressing DARPP-32, indicating that ZNRD1 may be important in the DARPP-32-mediated MDR of gastric cancer. DARPP-32 was also able to significantly decrease the anti-apoptotic activity of SGC7901/ADR cells. Further study of the biological functions of DARPP-32 may be helpful for understanding the mechanisms of MDR of gastric cancer cells and developing possible strategies to treat gastric cancer.
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http://dx.doi.org/10.1007/s10620-007-9829-xDOI Listing
January 2008

Reversal of multidrug resistance of vincristine-resistant gastric adenocarcinoma cells through up-regulation of DARPP-32.

Cell Biol Int 2007 Sep 21;31(9):1010-5. Epub 2007 Mar 21.

State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Changlexi ST 15, Xi'an 710032, Shaanxi Province, China.

Here we investigated the roles of DARPP-32 in multidrug resistance (MDR) of gastric cancer cells and the possible underlying mechanisms. We constructed the eukaryotic expression vector of DARPP-32 and transfected it into human vincristine-resistant gastric adenocarcinoma cell line SGC7901/VCR. Up-regulation of DARPP-32 could significantly enhance the sensitivity of SGC7901/VCR cells towards vincristine, adriamycin, 5-fluorouracil and cisplatin, and could decrease the capacity of cells to efflux adriamycin. What's more, the results of subrenal capsule assay confirmed that DARPP-32 might play a certain role in MDR of gastric cancer. DARPP-32 could significantly down-regulate the expression of P-gp and zinc ribbon domain-containing 1 (ZNRD1), but not alter the expression of multidrug resistance-associated protein (MRP) or the glutathione S-transferase (GST). DARPP-32 could also significantly decrease the anti-apoptotic activity of SGC7901/VCR cells. Further study of the biological functions of DARPP-32 might be helpful for understanding the mechanisms of MDR in gastric cancer.
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http://dx.doi.org/10.1016/j.cellbi.2007.03.020DOI Listing
September 2007

Mechanisms of growth arrest by zinc ribbon domain-containing 1 in gastric cancer cells.

Carcinogenesis 2007 Aug 26;28(8):1622-8. Epub 2007 Mar 26.

State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032 Shaanxi Province, China.

Previous studies by our laboratory indicated that zinc ribbon domain-containing 1 (ZNRD1) suppressed the growth of gastric cancer cells with a G(1) cell cycle arrest. However, the precise molecular mechanism underlying the growth-inhibitory effect of ZNRD1 remained fragmentary. In the present study, we have demonstrated that ZNRD1 could significantly inhibit the in vitro and in vivo growth of gastric cell line MKN28. Human cDNA microarray, reverse transcription-polymerase chain reaction and western blot analyses were used to identify differentially expressed cell cycle-related genes in MKN28 cells over-expressing ZNRD1. ZNRD1-induced growth suppression was found at least partially to regulate various proteins and signaling pathways controlling G(1) to S progression, including inhibition of cyclin D1 and CDK4, up-regulation of p21(CIP1/WAF1) and p27(Kip1) and acceleration of pRb dephosphorylation. Furthermore, ZNRD1 significantly inhibited the transcriptional activity of cyclin D1. p27(Kip1) might play a pivotal role in ZNRD1-induced cell cycle arrest because the p27(Kip1) anti-sense could block the cytostatic effects of ZNRD1. Moreover, ZNRD1 suppressed Skp2 expression via an increase in the protein instability, and induced significant decrease in cyclin E-CDK2 kinase activity. In addition, ZNRD1 could reduce tumor microvessel densities through inhibition of VEGF. Taken together, these results suggested that ZNRD1 might inhibit cell growth by targeting cell cycle-related genes and reducing tumor angiogenesis.
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http://dx.doi.org/10.1093/carcin/bgm064DOI Listing
August 2007