Li Yu

Sun Yat-Sen University, Shengcheng, Guangdong, China

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Publications (11)41.44 Total impact

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    ABSTRACT: Aims: To investigate the alterations in miRNA expression during the progression of dysplasia in cervical epithelium. Methods: A global miRNA expression profile of normal cervical squamous epithelium (Normal), cervical intraepithelial neoplasia (CIN) 3 and invasive squamous cell carcinoma (ISCC) was produced using the seventh generation of the miRCURY™ LNA microRNA Array (Exiqon, Vedbaek, Denmark). The reliability of miRNA arrays was verified by reverse transcription PCR. Results: Normal, CIN 3 and ISCC showed distinct miRNA expression profiles. The differentially expressed miRNAs in ISCC versus CIN 3 clearly differed from that in CIN 3 versus Normal. Compared with ISCC versus Normal, more identical miRNAs were found in ISCC versus CIN 3 than in CIN 3 versus Normal. Conclusion: A particular set of miRNAs was associated with the progression of normal cervical epithelium to CIN 3 and CIN 3 to ISCC. The miRNA profile changed more noticeably in the progression of CIN to ISCC than normal cervical epithelium to CIN.
    Future Oncology 02/2014; · 3.20 Impact Factor
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    ABSTRACT: Aberrant expression of high mobility group box 1 (HMGB1) is associated with tumor development and progression. The current study was conducted to evaluate the significance of HMGB1 immunostaining on cell block (CB) preparations in the diagnosis of neoplastic and preneoplastic lesions of the cervix. The CBs were prepared from 157 residual liquid-based gynecologic cytology specimens which were collected from women whose cervical lesions had been confirmed by histopathology. The expression of HMGB1 and p16INK4A (p16) was visualized by immunocytochemistry on the CB preparations, and the association of their expression patterns was correlated with the severity of cervical lesions. HeLa cells were used as positive control. HMGB1 expression was observed in dysplastic and neoplastic cells and increased along with the progression of cervical neoplasia. The rates of positive staining for HMGB1 in cervical intraepithelial neoplasia 1 (CIN-1), CIN-2, CIN-3, and invasive squamous cell carcinomas (ISCCs) were 69.4, 96.9, 100.0, and 100.0%, respectively. The differences between positive rates of patients with chronic cervicitis and various CINs as well as ISCCs were significant (P < 0.005). The differences in positive staining rates between each two CIN groups, and differences between CIN-1/2 and ISCCs, were also significant (P < 0.005). The expression pattern of HMGB1 was generally correlated with that of p16 (P < 0.001). HMGB1 staining was observed in some p16-negative specimens. HMGB1 immunostaining on a CB from gynecologic cytology specimens is potentially valuable for the screening of cervical lesions in cases with questionable cytology. Diagn. Cytopathol. 2014. © 2014 Wiley Periodicals, Inc.
    Diagnostic Cytopathology 02/2014; · 1.49 Impact Factor
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    ABSTRACT: Endometrial adenocarcinoma is the most common tumour of the female genital tract in developed countries, and oestrogen receptor (ER) signalling plays a pivotal role in its pathogenesis. When we used bioinformatics tools to search for the genes contributing to gynecological cancers, the expression of Olfactomedin 4 (OLFM4) was found by digital differential display to be associated with differentiation of endometrial adenocarcinoma. Aberrant expression of OLFM4 has been primarily reported in tumours of the digestive system. The mechanism of OLFM4 in tumuorigenesis is elusive. We investigated OLFM4 expression in endometrium, analysed the association of OLFM4 with ER signalling in endometrial adenocarcinoma, and examined the roles of OLFM4 in endometrial adenocarcinoma. Expression of OLFM4 was increased during endometrial carcinogenesis, linked to the differentiation of endometrioid adenocarcinoma, and positively related to the expression of oestrogen receptor-α (ERα) and progesterone receptor. Moreover, ERα-mediated signalling regulated expression of OLFM4, and knockdown of OLFM4 enhanced proliferation, migration and invasion of endometrial carcinoma cells. Down-regulation of OLFM4 was associated with decreased cumulative survival rate of patients with endometrioid adenocarcinoma. Our data suggested that impairment of ERα signal-mediated OLFM4 expression promoted the malignant progression of endometrioid adenocarcinoma, which may have significance for the therapy of this carcinoma.
    Journal of Cellular and Molecular Medicine 02/2014; · 4.75 Impact Factor
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    ABSTRACT: As a major class of pattern-recognition receptors, Toll-like receptors (TLRs), play a critical role in defense against invading pathogens. Increasing evidence demonstrates that, in addition to infection, TLRs are involved in other important pathological processes, such as tumorigenesis. Activation of TLRs results in opposing outcomes, pro-tumorigenic effects and anti-tumor functions. TLR signaling can inhibit apoptosis and promote chronic inflammation-induced tumorigenesis. TLR activation in tumor cells and immune cells can induce production of cytokines, increase tumor cell proliferation and apoptosis resistance, promote invasion and metastasis, and inhibit immune cell activity resulting in tumor immune escape. In contrast, the engagement of other TLRs directly induces growth inhibition and apoptosis of tumor cells and triggers activation of immune cells enhancing anti-tumor immune responses. Thus, the interpretation of the precise function of each TLR in tumors is very important for targeting TLRs and using TLR agonists in tumor therapy. We review the role of TLR signaling in tumors and discuss the factors that affect outcomes of TLR activation.
    Biochimica et Biophysica Acta 12/2012; · 4.66 Impact Factor
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    ABSTRACT: Toll-like receptors (TLRs) are a class of pattern recognition receptors sensing microbial components and triggering an immune response against pathogens. In addition to their role in anti-infection immunity, increasing evidence indicates that engagement of TLRs can promote cancer cell survival and proliferation, induce tumor immune evasion, and enhance tumor metastasis and chemoresistance. Recent studies have demonstrated that endogenous molecules or damage-associated molecular patterns released from damaged/necrotic tissues are capable of activating TLRs and that the endogenous ligands-mediated TLR signaling is implicated in the tumor development and affects the therapeutic efficacy of tumors. Since both exogenous and endogenous TLR ligands can initiate TLR signaling, which is the most valuable player in tumor development becomes an interesting question. Here, we summarize the effect of TLR signaling on the development and progression of tumors, and discuss the role of exogenous and endogenous TLR ligands in the tumorigenesis.
    Cellular and Molecular Life Sciences CMLS 11/2011; 69(6):935-49. · 5.62 Impact Factor
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    ABSTRACT: Olfactomedin 4 (OLFM4) is expressed in gastrointestinal cancers and related to progression and differentiation of these malignancies. However, whether OLFM4 contributes to tumorigenesis of other tissues has not been thoroughly investigated. The purpose of the study was to investigate OLFM4 expression in cervical epithelium and its association with progression of cervical neoplasia and differentiation of cervical carcinomas. Immunohistochemistry and real-time reverse transcription-polymerase chain reaction were used to evaluate the expression and distribution of OLFM4 in cervical intraepithelial neoplasia (CIN) and invasive squamous cell carcinomas (ISCCs). The overall positive OLFM4 staining levels in normal cervical epithelia, CIN I, CIN II, CIN III, and ISCCs are 22.0%, 94.2%, 93.7%, 94.6%, and 96.7%, respectively. The intensity of OLFM4 staining was enhanced according to increased pathologic grade of cervical squamous intraepithelial lesion. The immunoreactivity to OLFM4 was stronger in well-differentiated ISCCs than in poorly differentiated ISCCs. Olfactomedin 4 expression has been associated with progression of CIN and differentiation of cervical cancer. The results provide new evidence that OLFM4 plays an important role in tumorigenesis in the female reproductive tract.
    International Journal of Gynecological Cancer 02/2011; 21(2):367-72. · 1.94 Impact Factor
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    ABSTRACT: Toll-like receptors (TLRs), a family of pattern recognition receptors, recognize and respond to conserved components of microbes and play a crucial role in both innate and adaptive immunity. In addition to binding exogenous ligands derived from pathogens, TLRs interact with endogenous molecules released from damaged tissues or dead cells and regulate many sterile inflammation processes. Putative endogenous TLR ligands include proteins and peptides, polysaccharides and proteoglycan, nucleic acids and phospholipids, which are cellular components, particularly extracellular matrix degradation products. Accumulating evidence demonstrates that endogenous ligand-mediated TLR signalling is involved in pathological conditions such as tissue injury, repair and regeneration; autoimmune diseases and tumorigenesis. The ability of TLRs to recognize endogenous stimulators appears to be essential to their function in regulating non-infectious inflammation. In this review, we summarize current knowledge of endogenous TLR ligands and discuss the biological significance of TLR signalling triggered by endogenous ligands in several sterile inflammation conditions.
    Journal of Cellular and Molecular Medicine 11/2010; 14(11):2592-603. · 4.75 Impact Factor
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    ABSTRACT: This study was conducted to evaluate the reliability and role of cell block preparations in the diagnosis of neoplastic and preneoplastic lesions of the cervix and to improve the value of cell block preparations in diagnosing and predicting the prognosis of cervical lesions through immunostaining of p16INK4A (p16), Ki-67, and human papillomavirus (HPV) L1 capsid protein (HPV L1). In total, 138 specimens were diagnosed on liquid-based cytology (LBC) and cell block preparations, and 63 specimens were subjected subsequently to tissue follow-up and immunostaining for p16, Ki-67, and HPV L1 on cell block sections. In 42 specimens that were diagnosed as low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion (HSIL), and squamous cell carcinoma (SCC) on cell blocks, 38 specimens (90.5%) were confirmed by histopathologic reports, and there was slightly better than 81.6% agreement between LBC and tissue follow-up. Immunointensity and cells that were positive for p16 were enhanced according to increased pathologic grade and differed statistically between cervical intraepithelial neoplasia 1 (CIN-1) and CIN-2/CIN-3 as well as SCC. The positive rates of HPV L1 decreased gradually according to the severity of cervical neoplasia, and HPV L1/p16 expression patterns were related to the severity of cervical lesions. The cell block preparation technique was complementary to LBC, and the authors concluded that the application of LBC combined with cell block preparations may improve the diagnostic accuracy of cytology. Immunostaining for p16 and Ki-67 on cell block preparations can help to improve the diagnostic accuracy of HSIL and SCC. A combined expression pattern of p16 and HPV L1 may serve as a valuable index for predicting prognosis and follow-up of cervical dysplastic lesions.
    Cancer Cytopathology 02/2010; 118(1):47-55. · 4.43 Impact Factor
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    ABSTRACT: Chronic infection and inflammation are among the most important factors contributing to cancer development and growth. Toll-like receptors (TLRs) are important families of pattern recognition receptors, which recognize conserved components of microbes and trigger the immune response against invading microorganisms. TLR4 is the signaling receptor for lipopolysaccharide (LPS), the endotoxic component of Gram-negative bacteria. Recent studies demonstrate that TLRs are expressed in some tumor cells, and that the expression of TLRs in these cells is associated with tumorigenesis. Cervical intraepithelial neoplasia (CIN) is a key stage in the development of cervical cancer and human papillomavirus (HPV) infection is an essential factor in cervical carcinogenesis. As the cervix is in constant contact with bacteria, especially Gram-negative bacteria, we hypothesize that TLR4-mediated bacterial stimulation may be involved in the tumorigenesis of cervical cancer. In the present study, the expression and distribution of TLR4 in CIN and cervical squamous carcinoma were investigated by immunohistochemistry. To our surprise, we observed a decrease in the expression of TLR4 during the progression of cervical neoplasia and this down-regulation of TLR4 appeared to be associated with the expression of P(16INK4A) which is a crucial marker of HPV integration into host cells. These data offer further insight regarding the association of HPV infection and TLR signaling during the carcinogenesis of cervical cancer.
    Cancer Immunology and Immunotherapy 02/2010; 59(7):1021-8. · 3.64 Impact Factor
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    ABSTRACT: Toll-like receptors are an important family of pattern recognition receptors. They recognize microbial conserved components and trigger protective responses to the invading pathogens, which constitute a major part of the innate immune system. Toll-like receptors are mainly expressed in immune cells. The current evidences demonstrate that Toll-like receptors are present in some epithelial cells and epithelium derived tumor cells. The expression of Toll-like receptors in these cells is related to infection and inflammation, and tumor progression as well. Genital mucosal epithelium is the first line in defense of microorganism invasion in the female reproductive tract. Toll-like receptors expressed in the genital tract have been implicated in many aspects of reproductive physiology and pathology in the female. In the current review, we will focus on the expression of Toll-like receptors in the female genital mucosa and its association with anti-infection immunity and tumorigenesis.
    American Journal Of Reproductive Immunology 08/2009; 62(1):1-8. · 3.32 Impact Factor
  • Li Yu, Shangwu Chen
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    ABSTRACT: Toll-like receptors (TLRs), mainly expressing in human immune related cells and epithelial cells, play an essential role in the host defense against microbes by recognizing conserved bacterial molecules. Recently, the expression or up-regulation of TLRs has been detected in many tumor cell lines or tumors, especially epithelial derived cancers. Although the TLR profile varies on different tumor cells, the current evidences indicate that the expression of TLRs is functionally associated with tumor progression. TLR expression may promote malignant transformation of epithelial cells. Engagement of TLRs increases tumor growth and tumor immune escape, and induces apoptosis resistance and chemoresistance in some tumor cells. These findings demonstrate that TLR is a promising target for the development of anticancer drugs and make TLR agonists or antagonists the potential agents for tumor therapy.
    Cancer Immunology and Immunotherapy 10/2008; 57(9):1271-8. · 3.64 Impact Factor