Xia Zhao

Publications of Xia Zhao

• Autophagy in tumorigenesis and cancer therapy: Dr Jekyll or Mr Hyde?

  Authors: Shengtao Zhou, Manchao Kuang, Bingjie Zhang, Linjie Zhao, Zhu Liang, Tao Yi, Canhua Huang, Xia Zhao, Yuquan Wei

  Cancer Letters. 12/2012;

  Autophagy is an evolutionarily conserved mechanism for intracellular substance degradation, responsible for the recycling of metabolic substances and the maintenance of intracellular stability. ItAutophagy is an evolutionarily conserved mechanism for intracellular substance degradation, responsible for the recycling of metabolic substances and the maintenance of intracellular stability. It has early been demonstrated to play a significant role in tumorigenesis, but whether it acts as a promoter or a suppressor during tumorigenesis seems to be context-specific. Moreover, autophagy is also implicated in promoting chemoresistance of cancer cells so as to attenuate therapeutic efficacy of chemotherapy. On the contrary, other reports highlight a tumor-killing role of autophagy during cancer treatment. Herein, this review aims to revisit the key features of autophagy, summarize the seemingly contradictory roles of autophagy during both tumorigenesis and cancer chemotherapy, and evaluate the feasibility of altering the level of cellular autophagy as part of cancer adjuvant treatment.

• Proteomics identification of annexin A2 as a key mediator in the metastasis and proangiogenesis of endometrial cells in human adenomyosis

  Authors: Shengtao Zhou, Tao Yi, Rui Liu, Ce Bian, Xiaorong Qi, Xiang He, Kui Wang, Jingyi Li, Xia Zhao, Canhua Huang, Yuquan Wei

  Molecular and Cellular Proteomics. 06/2012;

  Adenomyosis is a common estrogen-dependent disorder of females characterized by a downward extension of the endometrium into the uterine myometrium and neovascularization in ectopic lesions. ItAdenomyosis is a common estrogen-dependent disorder of females characterized by a downward extension of the endometrium into the uterine myometrium and neovascularization in ectopic lesions. It accounts for chronic pelvic pain, dysmenorrhea, menorrhagia and infertility in 8.8-61.5% women worldwide. However, the molecular mechanisms for adenomyosis development remain poorly elucidated. Here, we utilized a 2-DE/MS-based proteomics analysis to compare and identify differentially expressed proteins in matched ectopic and eutopic endometrium of adenomyosis patients. A total of 93 significantly altered proteins were identified by tandem MS analysis. Further cluster analysis revealed a group of estrogen-responsive proteins as dysregulated in adenomyosis, among which annexin A2, a member of annexin family proteins, was found up-regulated most significantly in the ectopic endometrium of adenomyosis compared with its eutopic counterpart. Overexpression of ANXA2 was validated in ectopic lesions of human adenomyosis and was found to be tightly correlated with markers of epithelial-to-mesenchymal transition and dysmenorrhea severity of adenomyosis patients. Functional analysis demonstrated that estrogen could remarkably up-regulate ANXA2 and induce epithelial-to-mesenchymal transition in an in vitro adenomyosis model. Enforced expression of ANXA2 could mediate phenotypic mesenchymal-like cellular changes, with structural and functional alterations in a β-catenin/Tcf signaling-associated manner, which could be reversed by inhibition of ANXA2 expression. We also proved that enforced expression of ANXA2 enhanced the proangiogenic capacity of adenomyotic endometrial cells through HIF-1α/VEGF-A pathway. In vivo, we demonstrated that ANXA2 inhibition abrogated endometrial tissue growth, metastasis and angiogenesis in an adenomyosis nude mice model and significantly alleviated hyperalgesia. Taken together, our data unraveled a dual role for ANXA2 in the pathogenesis of human adenomyosis through conferring endometrial cells both metastatic potential and proangiogenic capacity, which could serve as a potential therapeutic target for the treatment of adenomyosis patients.

• Orlistat, a novel potent antitumor agent for ovarian cancer: proteomic analysis of ovarian cancer cells treated with Orlistat.

  Authors: Hui-Qiong Huang, Jing Tang, Sheng-Tao Zhou, Tao Yi, Hong-Ling Peng, Guo-Bo Shen, Na Xie, Kai Huang, Tao Yang, Jin-Hua Wu, Can-Hua Huang, Yu-Quan Wei, Xia Zhao

  International journal of oncology. 05/2012;

  Orlistat is an orally administered anti-obesity drug that has shown significant antitumor activity in a variety of tumor cells. To identify the proteins involved in its antitumor activity, weOrlistat is an orally administered anti-obesity drug that has shown significant antitumor activity in a variety of tumor cells. To identify the proteins involved in its antitumor activity, we employed a proteomic approach to reveal protein expression changes in the human ovarian cancer cell line SKOV3, following Orlistat treatment. Protein expression profiles were analyzed by 2-dimensional polyacrylamide gel electrophoresis (2-DE) and protein identification was performed on a MALDI-Q-TOF MS/MS instrument. More than 110 differentially expressed proteins were visualized by 2-DE and Coomassie brilliant blue staining. Furthermore, 71 proteins differentially expressed proteins were positively identified via mass spectrometry (MS)/MS analysis. In particular, PKM1/2, a key enzyme involved in tumorigenesis, was found to be significantly downregulated in SKOV3 cells following treatment with Orlistat. Moreover, PKM1/2 was proved to be downregulated in SKOV3 cells by western blot analysis after treatment with Orlistat. Taken together, using proteomic tools, we identified several differentially expressed proteins that underwent Orlistat-induced apoptosis, particularly PKM2. These changes confirmed our hypothesis that Orlistat is a potential inhibitor of ovarian cancer and can be used as a novel adjuvant antitumor agent.

• Live-attenuated measles virus vaccine confers cell contact loss and apoptosis of ovarian cancer cells via ROS-induced silencing of E-cadherin by methylation.

  Authors: Shengtao Zhou, Yuhua Li, Fuqiang Huang, Boya Zhang, Tao Yi, Zhengyu Li, Hong Luo, Xiang He, Qian Zhong, Ce Bian, Xiaojuan Lin, Xiaorong Qi, Ping Liu, Canhua Huang, Xia Zhao, Yuquan Wei

  Cancer letters. 05/2012; 318(1):14-25.

  Herein we present a novel molecular mechanism of the antitumor effects of live-attenuated measles virus (MV) vaccine in ovarian cancer. Using a 2-DE/MS-based comparative proteomics strategy, weHerein we present a novel molecular mechanism of the antitumor effects of live-attenuated measles virus (MV) vaccine in ovarian cancer. Using a 2-DE/MS-based comparative proteomics strategy, we identified 17 proteins differentially expressed in live-attenuated MV vaccine-treated SKOV-3 ovarian cancer cells, including oxidative stress-associated enzymes and cell contact-related proteins, which indicated that live-attenuated MV vaccine could induce aberrant ROS activation. It further mediated epigenetic silencing of E-cadherin via upregulating DNMT3a that conferred both cell-cell and cell-matrix contact loss and apoptosis of ovarian cancer cells. This process could be reversed through ROS inhibition. Our study lays the theoretical foundation for the clinical application of live-attenuated MV vaccine as a potential oncotherapeutic agent for ovarian cancer treatment.

• Autophagy in tumorigenesis and cancer therapy: Dr Jekyll or Mr Hyde?

  Authors: Shengtao Zhou, Manchao Kuang, Bingjie Zhang, Linjie Zhao, Zhu Liang, Tao Yi, Canhua Huang, Yuquan Wei, Xia Zhao

  Cancer letters. 04/2012;

  Autophagy is an evolutionarily conserved mechanism for intracellular substance degradation, responsible for the recycling of metabolic substances and the maintenance of intracellular stability. ItAutophagy is an evolutionarily conserved mechanism for intracellular substance degradation, responsible for the recycling of metabolic substances and the maintenance of intracellular stability. It has early been demonstrated to play a significant role in tumorigenesis, but whether it acts as a promoter or a suppressor during tumorigenesis seems to be context-specific. Moreover, autophagy is also implicated in promoting chemoresistance of cancer cells so as to attenuate therapeutic efficacy of chemotherapy. On the contrary, other reports highlight a tumor-killing role of autophagy during cancer treatment. Herein, this review aims to revisit the key features of autophagy, summarize the seemingly contradictory roles of autophagy during both tumorigenesis and cancer chemotherapy, and evaluate the feasibility of altering the level of cellular autophagy as part of cancer adjuvant treatment.

• Proteomics identification of annexin A2 as a key mediator in the metastasis and proangiogenesis of endometrial cells in human adenomyosis.

  Authors: Shengtao Zhou, Tao Yi, Rui Liu, Ce Bian, Xiaorong Qi, Xiang He, Kui Wang, Jingyi Li, Xia Zhao, Canhua Huang, Yuquan Wei

  Molecular & cellular proteomics : MCP. 04/2012;

  Adenomyosis is a common estrogen-dependent disorder of females characterized by a downward extension of the endometrium into the uterine myometrium and neovascularization in ectopic lesions. ItAdenomyosis is a common estrogen-dependent disorder of females characterized by a downward extension of the endometrium into the uterine myometrium and neovascularization in ectopic lesions. It accounts for chronic pelvic pain, dysmenorrhea, menorrhagia and infertility in 8.8-61.5% women worldwide. However, the molecular mechanisms for adenomyosis development remain poorly elucidated. Here, we utilized a 2-DE/MS-based proteomics analysis to compare and identify differentially expressed proteins in matched ectopic and eutopic endometrium of adenomyosis patients. A total of 93 significantly altered proteins were identified by tandem MS analysis. Further cluster analysis revealed a group of estrogen-responsive proteins as dysregulated in adenomyosis, among which annexin A2, a member of annexin family proteins, was found up-regulated most significantly in the ectopic endometrium of adenomyosis compared with its eutopic counterpart. Overexpression of ANXA2 was validated in ectopic lesions of human adenomyosis and was found to be tightly correlated with markers of epithelial-to-mesenchymal transition and dysmenorrhea severity of adenomyosis patients. Functional analysis demonstrated that estrogen could remarkably up-regulate ANXA2 and induce epithelial-to-mesenchymal transition in an in vitro adenomyosis model. Enforced expression of ANXA2 could mediate phenotypic mesenchymal-like cellular changes, with structural and functional alterations in a β-catenin/Tcf signaling-associated manner, which could be reversed by inhibition of ANXA2 expression. We also proved that enforced expression of ANXA2 enhanced the proangiogenic capacity of adenomyotic endometrial cells through HIF-1α/VEGF-A pathway. In vivo, we demonstrated that ANXA2 inhibition abrogated endometrial tissue growth, metastasis and angiogenesis in an adenomyosis nude mice model and significantly alleviated hyperalgesia. Taken together, our data unraveled a dual role for ANXA2 in the pathogenesis of human adenomyosis through conferring endometrial cells both metastatic potential and proangiogenic capacity, which could serve as a potential therapeutic target for the treatment of adenomyosis patients.

• Proteomics identification of annexin A2 as a key mediator in the metastasis and proangiogenesis of endometrial cells in human adenomyosis

  Authors: Shengtao Zhou, Tao Yi, Rui Liu, Ce Bian, Xiaorong Qi, Xiang He, Kui Wang, Jingyi Li, Xia Zhao, Canhua Huang, Yuquan Wei

  Molecular &amp Cellular Proteomics. 04/2012; DOI: 10.1074/mcp.M112.017988.

  Adenomyosis is a common estrogen-dependent disorder of females characterized by a downward extension of the endometrium into the uterine myometrium and neovascularization in ectopic lesions. ItAdenomyosis is a common estrogen-dependent disorder of females characterized by a downward extension of the endometrium into the uterine myometrium and neovascularization in ectopic lesions. It accounts for chronic pelvic pain, dysmenorrhea, menorrhagia and infertility in 8.8-61.5% women worldwide. However, the molecular mechanisms for adenomyosis development remain poorly elucidated. Here, we utilized a 2-DE/MS-based proteomics analysis to compare and identify differentially expressed proteins in matched ectopic and eutopic endometrium of adenomyosis patients. A total of 93 significantly altered proteins were identified by tandem MS analysis. Further cluster analysis revealed a group of estrogen-responsive proteins as dysregulated in adenomyosis, among which annexin A2, a member of annexin family proteins, was found up-regulated most significantly in the ectopic endometrium of adenomyosis compared with its eutopic counterpart. Overexpression of ANXA2 was validated in ectopic lesions of human adenomyosis and was found to be tightly correlated with markers of epithelial-to-mesenchymal transition and dysmenorrhea severity of adenomyosis patients. Functional analysis demonstrated that estrogen could remarkably up-regulate ANXA2 and induce epithelial-to-mesenchymal transition in an in vitro adenomyosis model. Enforced expression of ANXA2 could mediate phenotypic mesenchymal-like cellular changes, with structural and functional alterations in a β-catenin/Tcf signaling-associated manner, which could be reversed by inhibition of ANXA2 expression. We also proved that enforced expression of ANXA2 enhanced the proangiogenic capacity of adenomyotic endometrial cells through HIF-1α/VEGF-A pathway. In vivo, we demonstrated that ANXA2 inhibition abrogated endometrial tissue growth, metastasis and angiogenesis in an adenomyosis nude mice model and significantly alleviated hyperalgesia. Taken together, our data unraveled a dual role for ANXA2 in the pathogenesis of human adenomyosis through conferring endometrial cells both metastatic potential and proangiogenic capacity, which could serve as a potential therapeutic target for the treatment of adenomyosis patients.

• lin-28 homologue A (LIN28A) promotes cell cycle progression via the regulation of cyclin-dependent kinase 2 (CDK2), cyclin D1 (CCND1), and cell division cycle 25 homolog A (CDC25A) expression in cancer.

  Authors: Ning Li, Xiaomin Zhong, Xiaojuan Lin, Jinyi Guo, Lian Zou, Janos L Tanyi, Zhongjun Shao, Shun Liang, Li-Ping Wang, Wei-Ting Hwang, Dionyssios Katsaros, Kathleen Montone, Xia Zhao, Lin Zhang

  The Journal of biological chemistry. 03/2012;

  RNA-binding protein, LIN28A, regulates the translation and stability of a large number of mRNAs, as well as the biogenesis of certain miRNAs, in embryonic stem (ES) cells and developing tissues.RNA-binding protein, LIN28A, regulates the translation and stability of a large number of mRNAs, as well as the biogenesis of certain miRNAs, in embryonic stem (ES) cells and developing tissues. Increasing evidence indicates that LIN28A functions as an oncogene promoting cancer cell growth. However, there is little known about its molecular mechanism of cell cycle regulation in cancer. Using tissue microarrays, we found that strong LIN28A expression was reactivated in about 10% (7.1 to 17.1%) of epithelial tumors (six tumor types, n=369). Both in vitro and in vivo experiments demonstrate that LIN28A promotes cell cycle progression in cancer cells. Genome-wide RNA IP Chip experiments indicate that LIN28A binds to thousands of mRNAs, including a large group of cell cycle regulatory mRNAs in cancer and ES cells. Furthermore, the ability of LIN28A to stimulate translation of LIN28A-binding mRNAs, such as CDK2, was validated in vitro and in vivo. Finally, using a combined gene expression microarray and bioinformatics approach, we found that LIN28A also regulates CCND1 and CDC25A expression, and that this is mediated by inhibiting the biogenesis of let-7 miRNA. Taken together, these results demonstrate that LIN28A is reactivated in about 10% of epithelial tumors, and promotes cell cycle progression by regulation of both mRNA translation (let-7 independent) and miRNA biogenesis (let-7 dependent).

• Influence of Orai1 intervention on mouse airway epithelium reactions in vivo and in vitro.

  Authors: Lin Lin, Xia Zhao, Wenhong Yan, Weidong Qi

  Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 02/2012; 108(2):103-12.

  Orai1 is crucial for store-operated Ca2(+) entry and Ca2(+) release-activated Ca2(+) channel activities. However, little is known about its function in allergic diseases. To assess the influence ofOrai1 is crucial for store-operated Ca2(+) entry and Ca2(+) release-activated Ca2(+) channel activities. However, little is known about its function in allergic diseases. To assess the influence of Orai1 intervention on mouse airway epithelium reactions in vivo and in vitro. We used immunohistochemical staining, enzyme-linked immunosorbent assay, and real-time reverse transcription-polymerase chain reaction to evaluate Orai1 expression in nasal and tracheal mucosa epithelium of nonsensitized, control, and 2-aminoethoxydiphenyl borate (2-APB)-treated groups in vivo and in vitro. In addition, we analyzed concentrations of interleukin 1β, interleukin 6, macrophage inflammatory protein 2, and tumor necrosis factor α in nasal lavage fluid, bronchoalveolar lavage fluid, and culture supernatant and their messenger RNAs in nasal and tracheal mucosa and cultured nasal and tracheal epithelium. Administration of 2-APB into the nostrils suppressed Orai1 expression in nasal and tracheal mucosa of treated mice compared with that in control mice and restrained the mediators in nasal lavage fluid, bronchoalveolar lavage fluid, and airway mucosa of treated groups compared with those in control groups. Similarly, the 2-APB intervention also alleviated Orai1 and the production of the mediators in culture supernatant and cultured airway epithelium under allergic conditions. Our results indicate that 2-APB could effectively ameliorate reactions of upper and lower airway epithelial cells in mice in allergic states in vivo and in vitro.

• Sensitive Determination of Barbiturates in Biological Matrix by Capillary Electrophoresis Using Online Large-Volume Sample Stacking*

  Authors: Liu-Yin Fan, Ting He, Yun-Yun Tang, Wei Zhang, Chao-Jin Song, Xia Zhao, Xiao-Yu Zhao, Cheng-Xi Cao

  Journal of forensic sciences. 01/2012;

    In China, some forensic cases are caused by barbiturates. Thus, the determination of trace level barbiturates in body fluid is important for the poisoning investigation. In this study, an online  In China, some forensic cases are caused by barbiturates. Thus, the determination of trace level barbiturates in body fluid is important for the poisoning investigation. In this study, an online large-volume sample stacking (LVSS) with polarity switching in capillary electrophoresis (CE) was applied for the sensitive determination of barbiturates. This technique involves injecting a large volume of sample into a capillary and removing the sample matrix plug out of the capillary by reversing the polarity. Quantitation limit obtained was 0.048, 0.057, 0.039, and 0.015 μg/mL for secobarbital, amobarbital, barbital, and phenobarbital (signal-to-noise ratio = 9). By using LVSS, the stacking was simply achieved at 171.7-, 169.7-, 202.7-, and 169.1-fold for the above four barbiturates. The relative standard deviation values of intraday and interday were <2.11% and 4.69%, respectively. Recoveries were ranged from 83.7 to 105.2%. Finally, the trace analysis method was applied to the analysis of real forensic specimens and has achieved satisfactory results.

• Comprehensive proteomic analysis of host cell lipid rafts modified by HBV infection.

  Authors: Na Xie, Kai Huang, Tao Zhang, Yunlong Lei, Rui Liu, Kui Wang, Shengtao Zhou, Jingyi Li, Jinhua Wu, Hong Wu, Cao Deng, Xia Zhao, Edouard Collins Nice, Canhua Huang

  Journal of proteomics. 01/2012; 75(3):725-39.

  Lipid rafts are cholesterol- and sphingolipid-rich membrane microdomains that have been shown to participate in the entry, assembly and budding of various viruses. However, their involvement in HBVLipid rafts are cholesterol- and sphingolipid-rich membrane microdomains that have been shown to participate in the entry, assembly and budding of various viruses. However, their involvement in HBV replication remains poorly characterized. In a preliminary study, we observed that HBV release could be markedly impaired by methyl-β-cyclodextrin mediated depletion of cholesterol in lipid rafts, and that this effect could be reversed by replenishment of exogenous cholesterol, suggesting that lipid rafts play an important role in the HBV life cycle. To further understanding how HBV exploited host cell lipid rafts to benefit replication, comprehensive proteomic approaches were used to profile the proteome changes of host cell lipid rafts in response to HBV infection using 2DE-MS/MS, in combination with SILAC-based quantitative proteomics. Using these approaches, a total of 97 differentially expressed proteins were identified. Bioinformatics analysis suggested that multiple host cell pathways were involved in the HBV infection processes including signal transduction, metabolism, immune response, transport, vesicle trafficking, cell adhesion and cellular ion homeostasis. These data will provide valuable clues for further investigation of HBV pathogenesis.

• Mapping the high-throughput SEREX technology screening for novel tumor antigens.

  Authors: Shengtao Zhou, Tao Yi, Boya Zhang, Fuqiang Huang, Huiqiong Huang, Jing Tang, Xia Zhao

  Combinatorial chemistry & high throughput screening. 01/2012;

  Advances in novel tumor-associated antigen (TAA) screening strategy have accelerated the identification and characterization of biomarkers and potential target molecules for tumor subtyping,Advances in novel tumor-associated antigen (TAA) screening strategy have accelerated the identification and characterization of biomarkers and potential target molecules for tumor subtyping, diagnosis and therapeutics, which may facilitate early detection and diagnosis of the diseases individually and enhance treatment approaches for cancer. Over the past decades, a plethora of non-invasive methodologies dedicated to identify novel target molecules have been primarily focusing on the discovery of human tumor antigens recognized by the autologous antibody repertoire or cytotoxic T lymphocytes, among which serological analysis of recombinant cDNA expression libraries (SEREX) technology is chronologically first established and is of outstanding sensitivity and antigen coverage. This approach involves immunoscreening cDNA libraries extracted from fresh tumor tissues with sera from cancer patients to identify gene products recognized by IgG antibody. SEREX-defined clones can be directly sequenced and their expression profiles can be readily determined, allowing for immediate structural definition of the antigenic target and subsequent identification of TAAs and their cognate autoantibodies. This review is not only devoted to outline the SEREX technology and its advantages, drawbacks and recent modifications currently available for discovering provocative tumor antigens, but also to translate these SEREX-defined peptides into valuable cancer-specific signatures that would aid in the development of diagnostics, prognostics and therapeutics for cancer patients.

• Quantitative Proteomics for Cancer Biomarker Discovery.

  Authors: Shufang Liang, Zhizhong Xu, Xuejiao Xu, Xia Zhao, Canhua Huang, Yuquan Wei

  Combinatorial chemistry & high throughput screening. 01/2012;

  The mass spectrometry (MS)-based quantitative proteomics is powerful to discover disease biomarkers that can provide diagnostic, prognostic and therapeutic targets, and it also can address importantThe mass spectrometry (MS)-based quantitative proteomics is powerful to discover disease biomarkers that can provide diagnostic, prognostic and therapeutic targets, and it also can address important problems in clinical and translational medical research. The current status of MS-based quantification strategy and technical advances of several main quantitative assays (two-dimensional (2-D) gel-based methods，stable isotope labeling with amino acids in cell culture (SILAC), isotope-coded affinity tag (ICAT), the isobaric tags for relative and absolute quantification (iTRAQ),18O labeling，absolute quantitation and label-free quantitation) have been summarized and reviewed. At present, except 2-D gel-based methods, several stable isotope labeling quantitative techniques, including SILAC, ICAT and iTRAQ, etc, have been widely applied in identification of differential expression of proteins, post-translational modifications and protein-protein interactions in order to look for novel candidate cancer biomarkers from different physiological states of cells, body fluids or tissue samples. Also, the advantages and challenges of different quantitative proteomic approaches are discussed in identification and validation of candidate targets.

• Preventing postoperative abdominal adhesions in a rat model with PEG-PCL-PEG hydrogel.

  Authors: Bing Yang, ChangYang Gong, Xia Zhao, ShengTao Zhou, ZhengYu Li, XiaoRong Qi, Qian Zhong, Feng Luo, ZhiYong Qian

  International journal of nanomedicine. 01/2012; 7:547-57.

  Poly (ethylene glycol)-poly (ɛ-caprolactone)-poly (ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel has been demonstrated to be biocompatible and thermosensitive. In this study, its potential efficacyPoly (ethylene glycol)-poly (ɛ-caprolactone)-poly (ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel has been demonstrated to be biocompatible and thermosensitive. In this study, its potential efficacy and mechanisms of preventing postsurgical abdominal adhesions were investigated. PECE hydrogel was transformed into gel state from sol state in less than 20 seconds at 37°C. None of the animals treated with the hydrogel (n = 15) developed adhesions. In contrast, all untreated animals (n = 15) had adhesions that could only be separated by sharp dissection (P < 0.001). The hydrogel adhered to the peritoneal wounds, gradually disappeared from the wounds within 7 days, and transformed into viscous fluid, being completely absorbed within 12 days. The parietal and visceral peritoneum were remesothelialized in about 5 and 9 days, respectively. The hydrogel prevented the formation of fibrinous adhesion and the invasion of fibroblasts. Also, along with the hydrogel degradation, a temporary inflammatory cell barrier was formed which could effectively delay the invasion of fibroblasts during the critical period of mesothelial regeneration. The results suggested that PECE hydrogel could effectively prevent postsurgical intra-abdominal adhesions, which possibly result from the prevention of the fibrinous adhesion formation and the fibroblast invasion, the promotion of the remesothelialization, and the hydroflotation effect.

• Dissection of aberrant GPCR signaling in tumorigenesis--a systems biology approach.

  Authors: Jinhua Wu, Na Xie, Xia Zhao, Edouard C Nice, Canhua Huang

  Cancer genomics & proteomics. 01/2012; 9(1):37-50.

  The superfamily of G-protein-coupled receptors (GPCRs) is one of the largest mammalian protein families. It is involved in signal transduction and participates in the regulation of normalThe superfamily of G-protein-coupled receptors (GPCRs) is one of the largest mammalian protein families. It is involved in signal transduction and participates in the regulation of normal physiological function and pathological progression of a range of diseases. Recent studies have demonstrated that many aberrant GPCRs and their ligands are associated with tumorigenesis, angiogenesis and metastasis, which provides promising opportunities for drug discovery for cancer prevention and treatment. It is necessary to search for drug targets such as ligands of unknown GPCRs and better modulators of known GPCRs using high throughput screening approaches. Here, we review recent research advances in the identification of novel GPCRs and their protein interactions.

• Induction of cell migration in vitro by an electrospun PDGF-BB/PLGA/PEG-PLA nanofibrous scaffold.

  Authors: Xia Zhao, Michael Hadjiargyrou

  Journal of biomedical nanotechnology. 12/2011; 7(6):823-9.

  Electrospinning is a versatile technique used to fabricate potential tissue engineering scaffolds with a structure similar to the native extracellular matrix (ECM). In this study, Platelet-DerivedElectrospinning is a versatile technique used to fabricate potential tissue engineering scaffolds with a structure similar to the native extracellular matrix (ECM). In this study, Platelet-Derived Growth Factor (PDGF)-BB with BSA as a carrier protein was incorporated into an electrospun PLGA/PEG-PLA composite scaffold for induction of cell migration, an early process necessary for tissue regeneration and wound healing. Incorporating PDGF-BB into the fibers did not change the overall morphology of the scaffold, with the exception of a slight increase (approximately 12%) in the number of fibers with diameters ranging from 1-100 nm. Following a strong burst of release during the initial 24 hours, approximately 20% of the total incorporated PDGF-BB was released from the scaffold over 5 days, as determined by ELISA. The presence of the released PDGF-BB was also confirmed via SDS-PAGE. Using an in vitro agarose-cell migration assay with MC3T3 pre-osteoblastic cells, the preserved bioactivity of the released PDGF-BB was demonstrated via its ability to stimulate robust cell migration, equivalent to that of pure unincorporated (control) PDGF-BB. Overall, this study demonstrates that it is feasible to incorporate and deliver bioactive PDGF-BB via an electrospun scaffold for potential tissue repair applications, especially as a potent inducer of cell migration.

• Coexisting peritoneal tuberculosis and endometriosis masquerading as advanced stage ovarian cancer in a postpartum woman: a case report and review of literature.

  Authors: Shengtao Zhou, Boya Zhang, Fuqiang Huang, Juan Liu, Da Zhu, Xia Zhao

  European journal of obstetrics, gynecology, and reproductive biology. 12/2011; 159(2):484-5.

• Improving intraperitoneal chemotherapeutic effect and preventing postsurgical adhesions simultaneously with biodegradable micelles.

  Authors: Changyang Gong, Bing Yang, Zhiyong Qian, Xia Zhao, Qinjie Wu, Xiaorong Qi, Yujun Wang, Gang Guo, Bing Kan, Feng Luo, Yuquan Wei

  Nanomedicine : nanotechnology, biology, and medicine. 11/2011;

  The two major concerns after cytoreductive surgery of abdominal and pelvic malignancies are residual tumors and peritoneal adhesions, which are inevitable and have great impact on prognosis.The two major concerns after cytoreductive surgery of abdominal and pelvic malignancies are residual tumors and peritoneal adhesions, which are inevitable and have great impact on prognosis. Therefore, to improve the intraperitoneal chemotherapeutic effect and prevent postsurgical adhesions simultaneously after surgery, we developed a novel strategy that combines the controlled drug delivery system (CDDS) with an antiadhesion barrier. Biodegradable poly(ethylene glycol)-poly(ɛ-caprolactone)-poly(ethylene glycol) (PECE) copolymer formed micelles in water, which turned instantly into a nonflowing gel at body temperature as a result of micellar aggregation. Effectiveness of doxorubicin-loaded PECE micelles (Dox-M) in improving intraperitoneal chemotherapeutic effect and preventing adhesions was investigated. Subsequently, we established a novel mouse model for postsurgical residual tumors and peritoneal adhesions, in which Dox-M could improve intraperitoneal chemotherapeutic effect and prevent postsurgical peritoneal adhesions simultaneously. Thus, it is a promising strategy to combine the CDDS and barrier method to improve the intraperitoneal chemotherapeutic effect and prevent peritoneal adhesions simultaneously after surgery.

• Efficient inhibition of an intraperitoneal xenograft model of human ovarian cancer by HSulf-1 gene delivered by biodegradable cationic heparin-polyethyleneimine nanogels.

  Authors: Ping Liu, Maling Gou, Tao Yi, Chuan Xie, Xiaorong Qi, Shengtao Zhou, Hongxin Deng, Yuquan Wei, Xia Zhao

  Oncology reports. 11/2011; 27(2):363-70.

  The HSulf-1 (heparan sulfate 6-O-endosulfatase 1) gene is an important element that modulates the sulfation status of heparan sulfate proteoglycans (HSPGs), leading to the interference ofThe HSulf-1 (heparan sulfate 6-O-endosulfatase 1) gene is an important element that modulates the sulfation status of heparan sulfate proteoglycans (HSPGs), leading to the interference of HSPG-related signal transduction pathways. HSulf-1 plays a key role in regulating cell proliferation, tumorigenesis and angiogenesis. Recently, some studies have reported that HSulf-1 is a down-regulated gene in the majority of examined tumor types. In our present study, a recombinant plasmid DNA carrying HSulf-1-cDNA (pHSulf-1) was constructed. The antitumor effect of pHSulf-1 delivered by heparin-polyethyleneimine (HPEI) nanogels on human ovarian cancer and the possible mechanisms of the antitumor efficacy in vivo were further investigated. Heparin-polyethyleneimine (HPEI) nanogels, as a new safe non-viral gene delivery carrier, were prepared to deliver the plasmid expressing HSulf-1 into HSulf-1-deficient SKOV3 human ovarian cancer cells in vitro and in vivo. pHSulf-1 could be efficiently transfected into SKOV3 ovarian cancer cells by HPEI nanogels in vitro and in vivo. Stable expression of HSulf-1 in vitro and in vivo was verified by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Furthermore, a SKOV3 intraperitoneal ovarian carcinomatosis model was established to investigate the growth inhibition function of pHSulf-1 in nude mice. Tumor weight was measured. An anti-angiogenesis effect of pHSulf-1 in vivo was detected by CD31 immunostaining and alginate-encapsulate tumor cell assay. Assessment of apoptotic cells and proliferation index in tumor tissues were performed by TUNEL assay and Ki‑67 immunostaining. Intraperitoneal injection of pHSulf-1/HPEI complexes efficiently reduced tumor weight by approximately 87% compared with control groups (P<0.01). Meanwhile, reduction in angiogenesis, inhibition of cell proliferation, as well as induction of tumor cell apoptosis were observed, without apparent systemic toxic effects. Collectively, these observations provide the first evidence that pHSulf-1 delivered by HPEI nanogels may become a promising therapeutic strategy against human ovarian cancer.

• Hypoxia: the driving force of uterine myometrial stem cells differentiation into leiomyoma cells.

  Authors: Shengtao Zhou, Tao Yi, Kai Shen, Boya Zhang, Fuqiang Huang, Xia Zhao

  Medical hypotheses. 09/2011; 77(6):985-6.

  We propose that stem cells that display specific phenotypic and functional characteristics exist in human uterine myometrium. Under hypoxic circumstances, estrogen signaling pathways in certainWe propose that stem cells that display specific phenotypic and functional characteristics exist in human uterine myometrium. Under hypoxic circumstances, estrogen signaling pathways in certain myometrial stem cells are aberrantly activated, which leads to continuous differentiation of this portion of cells into leiomyoma cells. This process also protects the cells from undergoing physiological apoptotic or dedifferentiation. Therefore, we summarized some evidences for our bases and hypothesize that hypoxia may be the key contributor to the pathogenesis of leiomyoma through aberrant estrogen pathway activation of myometrial stem cells.