Beihua Kong

Shandong University, Chi-nan-shih, Shandong Sheng, China

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Publications (124)370.08 Total impact


  • No preview · Article · Feb 2016 · Scientific Reports
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    ABSTRACT: NK cells accumulate at the maternal-fetal interface (MFI) and play essential roles in maintaining immune tolerance during pregnancy. The mechanisms that facilitate NK cells tolerance to fetal tissue are largely unknown. T cell Ig and mucin domain-containing protein 3 (Tim-3) is a newly defined molecule with essential immunological function in many physiological and pathological processes. Recent study showed that Tim-3 was involved in the regulation of immune tolerance at MFI. However, whether Tim-3 regulates NK cells cytotoxicity toward trophoblasts is unclear. Here, we showed Tim-3 was mainly expressed by decidual NK cells (dNK) and Tim-3 level in dNK was higher than peripheral NK cells (pNK). Tim-3+ dNK expressed more levels of mature markers CD94 and CD69 than Tim-3- dNK cells and blocking Tim-3 significantly inhibited dNK IFN-γ and TNF-α secretion. Furthermore, we found TGF-β1 may contribute to such up-regulation of Tim-3 in NK cells. Interestingly, blocking Tim-3 enhanced NK cytotoxicity toward trophoblast cell line HTR-8 but not K562. We found HTR-8 expressed Tim-3 ligand Galectin-9, in contrast K562 did not. Small interfering RNA-mediated silencing of Galectin-9 expression enhanced NK cytotoxicity toward HTR-8. We further showed Tim-3/Galecin-9 inhibited NK cytotoxicity toward trophoblast partially via impairing the degranulation process. In addition, clinical data showed that abnormal Tim-3 level on pNK might be associated with recurrent spontaneous abortion (RSA). Thus, our data demonstrate Tim-3/Galectin-9 pathway maintains local tolerance by suppressing NK cytotoxicity toward trophoblasts which may represent a new immunologic tolerance mechanism at MFI.
    No preview · Article · Jan 2016 · PLoS ONE
  • Yanli Ban · Ying Zhao · Fen Liu · Baihua Dong · Beihua Kong · Xun Qu
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    ABSTRACT: Problem: To study the effect of indoleamine 2,3-dioxygenase (IDO) expressed in HTR-8/SVneo cells on NKG2D and NKp46 expression and cytotoxicity of decidual NK (dNK) and peripheral NK (pNK) cells. Method of study: CD56(+) dNK and pNK cells purified were cultured with HTR-8/SVneo cell conditioned medium (CM), 1-MT+HTR-8/SVneo cell CM, and complete RPMI 1640 medium (negative control) in vitro. The mRNA and protein expression of NKG2D and NKp46 in NK cells were then assessed by qRT-PCR and flow cytometry, respectively. Their cytotoxicity was evaluated with LDH assays, and TNF-α secretion was analyzed by ELISA. Results: For dNK cells, the mRNA and protein expression of NKp46 as well as NKG2D did not differ significantly among the three groups (P > 0.05), whereas for pNK cells, the expression level was significantly decreased in HTR-8/SVneo cell CM group than the other two groups (P < 0.01). Peripheral NK cells cultured with HTR-8/SVneo cell CM showed reduced cytotoxicity and TNF-α secretion than the other two groups (P < 0.01), although there were no significant differences among three groups for dNK cells (P > 0.05). Conclusion: IDO expressed by HTR-8/SVneo cells can down-regulate NKp46 and NKG2D expression and reduce cytotoxicity in pNK cells, and may contribute to keep dNK cytotoxicity at a low level, suggesting an important role for IDO in the maintenance of normal pregnancy.
    No preview · Article · Jan 2016 · American Journal Of Reproductive Immunology
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    ABSTRACT: J.W. has nothing to disclose. X.D. has nothing to disclose. Y.Y. has nothing to disclose. X.Y. has nothing to disclose. B.K. has nothing to disclose. L.C. has nothing to disclose.
    No preview · Article · Jan 2016 · Fertility and sterility
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    ABSTRACT: DNA methylation is clinically relevant to important tumorigenic mechanisms. This study evaluated the methylation status of candidate genes in cervical neoplasia and determined their diagnostic performance in clinical practice. Cervical cancer and normal cervix tissue was used to select the top 5 discriminating loci among 27 loci in 4 genes (CCNA1, CADM1, DAPK1, JAM3), and one locus of JAM3 (region M4) was identified and confirmed with 267 and 224 cervical scrapings from 2 independent colposcopy referral studies. For patients with atypical squamous cells of unknown significance and those with low-grade squamous intraepithelial lesion, with JAM3-M4 compared to a triage marker of hrHPV testing, the specificity for cervical intraepithelial neoplasia 3 CIN3 and cancer cases (CIN3+) / no neoplasia and CIN1 (CIN1-) was significantly increased, from 21.88 to 81.82 and 15.38 to 85.18, respectively. The corresponding positive predictive value (PPV) was increased from 26.47 to 57.14 and 18.52 to 63.64, respectively. For hrHPV-positive patients, compared to a triage marker of cytology testing, JAM3-M4 showed increased specificity and PPV, from 30.67 to 87.65 and 38.82 to 82.14, respectively. We assessed whether JAM3-M4 could distinguish productive from transforming CIN2; the coincidence rate of JAM3-M4 and P16 was as high as 60.5%.
    Preview · Article · Oct 2015 · Oncotarget
  • Xuantao Su · Shanshan Liu · Xu Qiao · Yan Yang · Kun Song · Beihua Kong
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    ABSTRACT: We develop a pattern recognition cytometric technique for label-free cell classification. Two dimensional (2D) light scattering patterns from single cells and cell aggregates are obtained with a static cytometer. Good performance of the cytometric setup is verified by comparing yeast cell experimental results with theoretical simulations. Adaptive boosting (AdaBoost) method (a machine learning algorithm) is adopted for the analysis of the 2D light scattering patterns. It is shown that aggregates of three yeast cells can be well differentiated from aggregates of four yeast cells by this pattern recognition cytometric technique. We demonstrate that the pattern recognition cytometry can perform label-free classification of normal cervical cells and HeLa cells with a high accuracy rate.
    No preview · Article · Oct 2015 · Optics Express
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    ABSTRACT: Background: Recently, it is found that T-helper (Th) 22 cells are involved in different types of autoimmune and tumor diseases. But, till now, no study has been carried out to understand the involvement of these cells in cervical cancer (CC). Methods: Flow cytometry was used to determine the expression of interferon gamma (IFN-γ), Interleukin-22 (IL-22), IL-17 in the peripheral blood of healthy controls (HC), CIN and cervical cancer patients. From peripheral blood mononuclear cells (PBMCs), mRNA expression levels of Aryl hydrocarbon receptor (AHR), RAR-related orphan receptor C (RORC), TNF-α and IL-6 were respectively determined. Using the method of ELISA, plasma concentrations of IL-22, IL-17 and TNF-α were examined. Results: Th22 and Th17 cells were elevated in CC and CIN patients. Th1 cells and the plasma concentrations of IL-22 in CC patients were significantly increased compared with HC. In CC patients, an increased prevalence of Th22 cells was associated with lymph node metastases. There was a positive correlation between Th22 and Th17 cells, but an approximately negative correlation between Th22 and Th1 cells in CC patients. The mRNA expression of RORC, TNF-α and IL-6 was significantly high in CC patients. Conclusions: Our results indicate that there is a higher circulatory frequency of Th22, Th17 and Th1 cells in CC which may conjointly participate in the pathogenesis and growth of CC.
    Preview · Article · Oct 2015 · BMC Cancer
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    ABSTRACT: High grade serous ovarian carcinoma (HGSC) is a DNA instable tumor and its precursor is commonly found originating from the fimbriated end of the fallopian tube secretory epithelial (FTSE) cells. The local stresses via ovulation and related inflammation are risks for HGSC. In this study, we examined the cellular and molecular responses of FTSE cells to stress. We found that excess intracellular reactive oxygen species (ROS) in normal FTSE cells upregulated a subset of microRNA expression (defined as ROSmiRs). Most ROSmiRs' expression and function were influenced and regulated by p53, and together they drove the cells into stress-induced premature senescence (SIPS). However, ROS-induced miR-182 is regulated by β-catenin, not by p53. In normal FTSE cells, miR-182 overexpression triggers cellular senescence by p53-mediated upregulation of p21. Conversely, in cells with p53 mutations, miR-182 overexpression no longer enhances p21 but functions as an "Onco-miR". p53 dysfunction is a prerequisite for miR-182-mediated tumorigenesis. In addition, we found that human follicular fluid could significantly induce intracellular ROS in normal FTSE cells. These findings suggest that ROS and p53 mutations may trigger a series of events, beginning with overexpressing miR-182 by ROS and β-catenin, impairing the DNA damage response, promoting DNA instability, bypassing senescence and eventually leading to DNA instable tumors in FTSE cells.
    Full-text · Article · Oct 2015 · Oncotarget
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    ABSTRACT: GADD45A (growth arrest and DNA damage 45 A) is the first stress-inducible gene identified to be a target of p53. However, no studies to date have assessed variants of the GADD45 gene and their potential relationship to tumor susceptibility. We investigated the association of the GADD45A (1506T>C) polymorphism with ovarian cancer development in 258 ovarian cancer patients and 332 age-matched healthy women as controls using sequence analysis. We found a statistically significant difference in the GADD45A (1506T>C) genotype distributions between the case and control groups (TT vs. TC vs. CC, P = 0.0021) and found that variant 1506T>C was significantly associated with an increased risk of ovarian cancer (P<0.001, OR = 1.71, 95% CI [1.28–2.29]). We observed a statistically significant effect between tumor histology (P = 0.032) and CA125 status (P = 0.021). Carrying the C allele (TC+CC) was associated with an increased risk of positive CA125 (OR = 3.20, 95% CI [1.15–8.71). Carrying the T allele (TT+TC) showed a significant correlation with both higher GADD45A mRNA expression and longer ovarian cancer RFS (relapse-free survival) and OS (overall survival). We are the first group to demonstrate that the GADD45A (1506T>C) polymorphism is associated with ovarian cancer susceptibility and prognosis. These data suggest that GADD45A (1506T>C) is a new tumor susceptibility gene and could be a useful molecular marker for assessing ovarian cancer risk and for predicting ovarian cancer patient prognosis.
    Preview · Article · Sep 2015 · PLoS ONE
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    ABSTRACT: Calcium-sensing receptor (CaSR) is a G-protein‑ coupled receptor that senses blood calcium. In vivo, CaSR is required for normal epidermal differentiation by mediating calcium signaling. CaSR was confirmed to be a tumor suppressor in colon and breast cancer. The single-nucleotide polymorphism (SNP) rs17251221, located on the intron, is a genetic variation of the CaSR gene. We analyzed rs17251221 in ovarian cancer using an allelic discrimination assay. Cycling probes were used for genotyping 290 ovarian cancer patients and 312 age-matched cancer-free females. rs17251221 and clinicopathological characteristics of ovarian cancer were analyzed statistically. The AG and GG genotypes were confirmed to appear in fewer cancer cases than in controls and the genotype distribution between cases and controls was statistically significant. The AG+GG genotype was correlated with low ovarian cancer risk, while rs17251221 was not associated with clinicopathological variables including age at diagnosis, tumor size, histologic type, pathological subtype, lymph node metastasis, CA-125 expression, clinical stage, or degree of differentiation. The rs17251221 polymorphism genotype was not correlated with survival in ovarian cancer. These results suggest that the G allele of the CaSR rs17251221 polymorphism is protective against ovarian cancer and the homozygous GG genotype may be a protective genotype as well. The rs17251221 may play an important role in the development of ovarian cancer and could be used as a biomarker for predicting ovarian cancer.
    No preview · Article · Aug 2015 · Oncology Reports
  • Li Yan · Xiaolin Liu · Aijun Yin · Yuyan Wei · Qifeng Yang · Beihua Kong
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    ABSTRACT: Although the anticancer effects of Huaier extract have been widely investigated, including anti-proliferate, anti-angiogenic and anti-metastatic activities, the mechanisms are not well understood. This study aimed to elucidate the inhibitory effect of Huaier extract on tumor growth in cervical cancer cells and its molecular mechanisms. Cell viability and motility were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony assays, migration, and invasive assays, respectively. The distribution of the cell cycle was analyzed by flow cytometry. Huaier inhibited cell viability of SiHa and C33A cells in a time- and dose-dependent manner; cell migration and invasiveness were also suppressed; Huaier was able to cause G2/M cell cycle arrest in C33A cells. The western blot results confirmed Huaier dose-dependently increased expression of phosphorylated c-Jun N-terminal kinase (JNK), p-38 and downregulated the expression of phosphorylated extracellular signal-regulated kinase (ERK) in a time- and dose-dependently manner. In vivo experiments showed that Huaier significantly suppressed the tumor volume of SiHa cell xenografts. These data suggest that Huaier may inhibit tumor proliferation in cervical cancer via the JNK/p38 signaling pathway.
    No preview · Article · Jul 2015 · International Journal of Oncology
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    ABSTRACT: Due to a poor understanding of tumorigenesis, ovarian cancers remain the most lethal gynecologic malignancy and cause horrific deaths. In the last decade, a new dualistic model for ovarian cancer was proposed, wherein ovarian serous cancers are classified as either high-grade or low-grade, with each having different tumorigenic processes, and pathologic and clinical features. Surprisingly, both high- and low-grade ovarian serous cancers were recently found to originate not in the ovaries, but rather from the secretory cells of the fallopian tube, mostly from the tubal fimbriated ends. In this article, we review the evidentiary basis for the aforementioned paradigm shift in the cell origin of ovarian serous cancers, as well as its potential clinical implications.
    No preview · Article · Jul 2015 · Histology and histopathology
  • Zhao Li · Liping Sun · Zaijun Lu · Xuantao Su · Qifeng Yang · Xun Qu · Li Li · Kun Song · Beihua Kong
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    ABSTRACT: Nanoparticles are promising novel drug delivery carriers that allow tumor targeting and controlled drug release. In the present study, we prepared poly butyl-cyanoacrylate nanoparticles (PBCA-NP) entrapped with hypocrellin B (HB) to improve the effect of photodynamic therapy (PDT) in ovarian cancer. An ovarian cancer ascites model using Fischer 344 rats and PBCA-NP entrapped with HB (HB-PBCA-NP) were formed successfully. The pharmacodynamic characteristics and biodistribution of the HB-PBCA-NP system were evaluated by comparison with HB dimethyl sulfoxide (HB-DMSO) and testing at various time-points following intraperitoneal drug administration. HB-PBCA-NP-based PDT combined with cytoreductive surgery was then administrated to the tumor-bearing animals. Kaplan-Meier survival analysis was performed to assess the therapeutic effect of the nanoparticle system. The serum HB concentration peaked 4 h after drug administration in the nanoparticle system, and 1 h with HB-DMSO. The peak exposure time of tumor tissues was also extended (4 vs. 2 h), and PBCA-NP remained present for much longer than HB-DMSO. Although PDT combined with surgery prolonged the survival time significantly compared with surgery alone (84 days, P<0.05), there was no significant difference in the survival time of animals that received either HB-PBCA-NP- or HB-DMSO-based PDT after cytoreductive surgery (99 vs. 95 days, P=0.293). PBCA-NP exhibited potential advantages in controlled drug release and tumor targeting, which was beneficial for HB-based PDT. PDT combined with surgery prolonged the survival time, suggesting that this might be an alternative treatment option for ovarian cancer.
    No preview · Article · Jul 2015 · International Journal of Oncology
  • Linyan Xie · Yan Yang · Xuming Sun · Xu Qiao · Qiao Liu · Kun Song · Beihua Kong · Xuantao Su
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    ABSTRACT: Conventional optical cytometric techniques usually measure fluorescence or scattering signals at fixed angles from flowing cells in a liquid stream. Here we develop a novel cytometer that employs a scanning optical fiber to illuminate single static cells on a glass slide, which requires neither microfluidic fabrication nor flow control. This static cytometric technique measures two dimensional (2D) light scattering patterns via a small numerical aperture (0.25) microscope objective for label-free single cell analysis. Good agreement is obtained between the yeast cell experimental and Mie theory simulated patterns. It is demonstrated that the static cytometer with a microscope objective of a low resolution around 1.30 μm has the potential to perform high resolution analysis on yeast cells with distributed sizes. The capability of the static cytometer for size determination with submicron resolution is validated via measurements on standard microspheres with mean diameters of 3.87 and 4.19 μm. Our 2D light scattering static cytometric technique may provide an easy-to-use, label-free, and flow-free method for single cell diagnostics. © 2015 International Society for Advancement of Cytometry. © 2015 International Society for Advancement of Cytometry.
    No preview · Article · Jun 2015 · Cytometry Part A
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    ABSTRACT: Current research has strongly proposed that contrary to prior beliefs, many ovarian epithelial cancers (OECs) do not, as their name suggests, originate in the ovaries. Recent findings regarding both high-grade and low-grade serous carcinomas has implicated the fallopian tube as a cell source for these OECs, but until now, there has been little insight into the cellular source for clear cell and endometrioid carcinomas. In this commentary review article, we aimed to discuss the new findings that support the possible contribution from the fallopian tube in clear cell and endometrioid carcinomas. Specifically, we have provided results that showcased ovarian surface epithelia (OSE) and ovarian epithelial inclusions (OEIs) as having mesothelial and tubal origins and have strongly recognized the secondary müllerian system and the ability for tubal epithelia to implant upon the ovarian surface as contributing to fallopian tube-derived OEIs (F-OEIs). We have provided initial indications of these F-OEIs and their relationship to endometriosis and then clear cell and endometrioid carcinomas and subsequently offer our new proposal of a probable tubal origin. This new proposal is a paradigm that drastically changes the understanding behind the origin of these OECs and has significant clinical implications in the near future.
    No preview · Article · Jun 2015 · American Journal of Cancer Research
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    ABSTRACT: Successful human pregnancy requires the maternal immune system to recognize and tolerate the semi-allogeneic fetus. Myeloid-derived suppressor cells (MDSCs), which are capable of inhibiting T-cell responses, are highly increased in the early stages of pregnancy. Although recent reports indicate a role for MDSCs in fetal-maternal tolerance, little is known about the expansion of MDSCs during pregnancy. In the present study, we demonstrated that the trophoblast cell line HTR8/SVneo could instruct peripheral CD14(+) myelomonocytic cells toward a novel subpopulation of MDSCs, denoted as CD14(+)HLA-DR(-/low) cells, with suppressive activity and increased expression of IDO1, ARG-1, and COX2. After interaction with HTR8/SVneo cells, CD14(+) myelomonocytic cells secrete high levels of CCL2, promoting the expression of signal transducer and activator of transcription 3. We utilized a neutralizing monoclonal antibody to reveal the prominent role of CCL2 in the induction of CD14(+)HLA-DR(-/low) MDSCs. In combination, the results of the present study support a novel role for the cross-talk between the trophoblast cell line HTR8/SVneo and maternal CD14(+) myelomonocytic cells in initiating MDSCs induction, prompting a tolerogenic immune response to ensure a successful pregnancy.Cellular & Molecular Immunology advance online publication, 1 June 2015; doi:10.1038/cmi.2015.41.
    No preview · Article · Jun 2015 · Cellular & molecular immunology
  • Lijie Wang · Beihua Kong
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    ABSTRACT: Studies investigating the association between matrix metalloproteinase-1 (MMP1) gene promoter 1607-base pair (bp) polymorphism and ovarian cancer risk have yielded conflicting results. We therefore carried out a meta-analysis of 754 ovarian cancer cases and 1184 controls from 5 published case-control studies. The strength of the association between MMP1 1607-bp polymorphism and ovarian cancer susceptibility was calculated using pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). The results suggest that no statistically significant associations exist between MMP1 1607-bp polymorphisms and ovarian cancer risk in all 4 genetic models (2G2G vs 1G1G: OR, 1.08; 95% CI, 0.81-1.43; P = 0.23; 1G2G vs 1G1G: OR, 1.06; 95% CI, 0.82-1.36; P = 0.15; 1G2G + 2G2G vs 1G1G: OR, 1.05; 95% CI, 0.83-1.34; P = 0.16; 2G2G vs 1G1G + 1G2G: OR, 0.98; 95% CI, 0.80-1.20; P = 0.84). In summary, this meta-analysis showed that the MMP1 1607-bp polymorphism is not associated with ovarian cancer risk.
    No preview · Article · May 2015 · International Journal of Gynecological Cancer
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    ABSTRACT: Pseudo-Meigs' syndrome is a syndrome rarely caused by leiomyomas. Elevated CA125 usually suggests malignancy of the ovary. No reported case of pseudo-Meigs' syndrome presenting with necrosis and mucinous degeneration of uterine cellular leiomyomas (CLs) and an elevated CA125 level was found upon a PubMed search. A 37-year-old woman presenting with massive ascites, bilateral pleural effusions and a pelvic mass measuring 20x18x10 cm is described. The pre-operative serum CA125 was 920.4 U/ml. After total abdominal hysterectomy and partial omentumectomy, the final pathologic diagnosis was CL with focal hemorrhage, necrosis and mucinous degeneration. The ascites and pleural effusion disappeared, and the CA125 level returned to normal in one month. Benign leiomyoma accompanied by pseudo-Meigs' syndrome and elevated serum CA125 can mimic a pelvic malignancy.
    No preview · Article · Apr 2015 · Oncology Reports
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    ABSTRACT: Struma ovarii is an uncommon ovarian teratoma comprised predominantly of mature thyroid tissue. The combination of pseudo-Meigs' syndrome, and elevation of CA 125 to the struma ovarii is a rare condition that can mimic ovarian malignancy. We reported a case of benign struma ovarii, presenting with the clinical features of advanced ovarian carcinoma: complex pelvic mass, gross ascites, bilateral pleural effusion and markedly elevated serum CA 125 levels. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Ascites and pleural effusion were not evident and the CA 125 levels returned to normal following surgical excision. A systematic review of reported cases of coexistent benign struma ovarii, pseudo-Meigs' syndrome and elevated serum CA 125 was performed. Struma ovarii accompanied by pseudo-Meigs' syndrome and elevated serum CA 125 should be considered in the differential diagnosis of ovarian epithelial cancer.
    Preview · Article · Feb 2015 · Oncology letters
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    ABSTRACT: Ovarian cancer is a highly invasive cancer with poor prognosis. Previous studies have revealed lots of connections between the invasiveness and epithelial-mesenchymal transition (EMT), which is common during the progression of ovarian cancer. MDC1, a mediator of DNA damage checkpoint, has recently been implicated as a potential oncogene. Here, in this article, we studied the role of MDC1 in ovarian cancer metastasis. First, in tissue samples, we found that high expression level of MDC1 was correlated with poor prognosis. Furthermore, MDC1 overexpression in ovarian cancer cells significantly increased migration and invasion. In contrast, silencing MDC1 reversed these processes. Consistently, nude mice xenograft confirmed that silencing MDC1 suppressed tumor metastasis in vivo. We further demonstrated that MDC1 induced EMT through modulation EMT markers such as E-cadherin, N-cadherin, and vimentin. Taken together, our findings suggest that MDC1 promotes ovarian cancer metastasis through the induction of EMT.
    Full-text · Article · Jan 2015 · Tumor Biology

Publication Stats

1k Citations
370.08 Total Impact Points

Institutions

  • 2002-2015
    • Shandong University
      • School of Medicine
      Chi-nan-shih, Shandong Sheng, China
  • 2014
    • Northwestern University
      • Department of Obstetrics and Gynecology
      Evanston, Illinois, United States
  • 2009-2014
    • University of Jinan (Jinan, China)
      Chi-nan-shih, Shandong Sheng, China
  • 2013
    • Huazhong University of Science and Technology
      Wu-han-shih, Hubei, China
  • 2012-2013
    • The University of Arizona
      • Department of Obstetrics and Gynecology
      Tucson, Arizona, United States
  • 2011-2012
    • University of Alberta
      • Department of Biomedical Engineering
      Edmonton, Alberta, Canada