Bai Y.,Southern Medical University |
Bai Y.,Sichuan Academy of Medical science |
Sun Y.,Southern Medical University |
Sun Y.,Guangdong Medical College |
And 7 more authors.
Oncotarget | Year: 2014
Secretagogin (SCGN) has recently been identified to play a crucial role in cell apoptosis, receptor signaling and differentiation. However, its clinical significance and functional roles in SCLC chemoresistance remain unknown. Here we examined the expression of SCGN in clinical samples from SCLC patients and evaluated its relation with clinical prognosis. Then up and down-regulation of SCGN were carried out in SCLC cell lines to assess its influence on chemoresistance. Furthermore, luciferase reporter assay was used to evaluate whether SCGN is a novel direct target of miR-494. Our results revealed that elevated expression of SCGN was correlated with the poorer prognosis of SCLC patients and the more significant correlation with chemosensitivity. We also found that knockdown of SCGN expression in H69AR and H446AR cells increased chemosensitivity via increasing cell apoptosis and cell cycle arrest of G0/G1 phase, while over-expression of SCGN reduced chemosensitivity in sensitive H69 and H446 cells. SCGN as a novel target of miR-494 by luciferase reporter assay, up-regulation of miR-494 can sensitize H69AR cells to chemotherapeutic drugs. These results suggest SCGN is involved in the chemoresistance of SCLC under the regulation of miR-494 and may be a potential biomarker for predicting therapeutic response in treatment SCLC.
Nong Y.Q.,Guangdong Women and Children Hospital
Journal of assisted reproduction and genetics | Year: 2013
To determine the role of aquaporin 3 (AQP3) isoform in early embryonic development and protecting embryos subjected to freeze-thawing for assisted reproduction, we investigated the expression and distribution of AQP3 in mouse embryos at different developmental stages before and after vitrification. Eight-cell embryos, morulae, and blastocysts were obtained from female mice that had been superovulated by controlled ovarian hyperstimulation. Immunofluorescence staining, laser confocal microscopy, and Western blot were used to determine the expression and distribution of AQP3 in preimplantation mouse embryos before and after vitrification. AQP3 was expressed at the 8-cell to blastocyst stage before and after vitrification. The expression and distribution of AQP3 was developmentally regulated at the 8-cell to blastocyst stage. The expression of AQP3 was significantly decreased in 8-cell embryos and early blastocysts after vitrification. However, at the morulae stage, the expression of AQP3 was increased after vitrification. The developmental and vitrification-dependent changes in AQP3 expression and distribution suggest that this transmembrane channel might regulate mouse embryo development and contribute to the protective response during vitrification.
Li Y.,Jinan University |
Li Y.,Southern Medical University |
Liu H.,Guangdong Women and Children Hospital |
Lai C.,Jinan University |
And 3 more authors.
Cell and Tissue Research | Year: 2013
We investigate the role of the Lin28/let-7a/c-Myc pathway in non-muscle invasive bladder cancer (NMIBC). Using RT-PCR, western blot and immunohistochemistry techniques, the levels of pre-let-7a, let-7a, Lin28 and c-Myc RNA and/or proteins were determined in samples of normal bladder tissue and bladder cancer. Expression of pre-let-7a was found to be negatively correlated with the pathological grade of bladder cancer, while let-7a showed a positive correlation with bladder cancer pathological grade. Expression of Lin28 RNA and protein was not significantly different between normal bladder tissue and low-grade transitional cell carcinoma of bladder (TCC) but the expression levels in high-grade TCC were remarkably increased. Expression of c-Myc RNA and protein was significantly higher in bladder cancer samples in comparison to normal bladder tissue without correlation with cancer differentiation. Expression of all the above RNAs and proteins showed no significant difference in Ta and T1 stages. The Lin28/let-7a/c-Myc pathway plays an important role in NMIBC. In particular, expression levels of let-7a correlate with the degree of cancer differentiation but not cancer stage. © 2013 Springer-Verlag Berlin Heidelberg.
Liang Z.,Guangdong Women and Children Hospital |
Wu L.,Guangdong Women and Children Hospital |
Fan L.,Hainan Women and Children Hospital |
Zhao Q.,Guangdong Women and Children Hospital
BMC Pediatrics | Year: 2015
Background: Evidence shows exposure to ambient air pollution during pregnancy was associated with an increased risk of adverse birth outcomes, such as preterm birth, low birth weight and intrauterine growth retardation, but the results for birth defects have been inconsistent. Methods: The data on birth defects was collected from the Birth Defects Monitoring Network of Haikou city. Air pollution data for PM10, SO2 and NO2 were obtained from Haikou Environmental Monitoring Center. Logistic regression analysis was used to evaluate these associations. Results: The risk of birth defects was related to PM10 levels (adjusted OR = 1.039; 95% CI = 1.016-1.063) and SO2 levels (adjusted OR = 0.843; 95% CI = 0.733-0.969) for the second month of pregnancy. In the third month of pregnancy, the risk of birth defects was also related to PM10 levels (adjusted OR = 1.066; 95% CI = 1.043-1.090) and SO2 levels (adjusted OR = 0.740; 95% CI = 0.645-0.850). Conclusion: The study provides evidence that exposure to PM10 and SO2 during the second and third month of pregnancy may associated with the risk of birth defects. © 2014 Liang et al.; licensee BioMed Central Ltd.
Xu L.-Q.,Guangdong Women and Children Hospital |
Huang Y.-W.,Sun Yat Sen University |
Luo R.-Z.,Sun Yat Sen University |
Zhang Y.-N.,Sun Yat Sen University
World Journal of Surgical Oncology | Year: 2015
Background: The objective of this study is to establish the retroperitoneal lymph node metastasis model of endometrial VX2 carcinoma in rabbits and observe of its metastatic features. Methods: The VX2 cells were transplanted into the uterine muscularis mucosae of 48 rabbits by injecting carcinoma mass suspension. According to time, the rabbits were killed after the transplantation of VX2 cells, and they were divided into six groups, 15-, 18-, 21-, 24-, 27-, and 30-day group, and six rabbits in each group. Control groups consisted of those receiving no treatment or an injection of saline. The specimens of transplanted endometrial carcinoma and retroperitoneal lymph node in the rabbits were examined histopathologically after they were killed. Results: All rabbits developed VX2 endometrial carcinoma which was confirmed with pathological examination. Significantly increased tumor volume was observed at day 24, 27, and 30 post-injection of VX2 cells (P < 0.05). The retroperitoneal lymph nodes were not enlarged completely in each rabbit in the 15-day group, partly enlarged in the 18- and 21-day group, and all enlarged in the 24-, 27-, and 30-day group. The histopathological examination revealed no complete retroperitoneal lymph node metastasis in the 15- and 18-day group, partial metastasis in the 21-day group, and complete metastasis in the 24-, 27-, and 30-day group. Conclusions: The model was established successfully by injecting carcinoma mass suspension, and various retroperitoneal lymph node metastasis model of endometrial VX2 carcinoma can be established rapidly in a month after the transplantation. © 2015 Xu et al.; licensee BioMed Central.
Liang L.,Southern Medical University |
Li X.,Southern Medical University |
Li X.,Guangdong Women and Children Hospital |
Zhang X.,Southern Medical University |
And 11 more authors.
Gastroenterology | Year: 2013
Background & Aims: Formin-like (FMNL)2 is up-regulated in colorectal tumors and has been associated with tumor progression, but little is known about regulatory mechanisms. We investigated whether microRNAs regulate levels of FMNL2 in colorectal cancer (CRC) cells. Methods: We used real-time polymerase chain reaction and immunoblot analyses to measure levels of miR-137, high-mobility group AT-hook (HMGA)1, and FMNL2 in CRC cells and tissue samples from patients (n = 50). We used luciferase reporter assays to determine the association between miR-137 and the FMNL2 3′ untranslated region, and HMGA1 and the miR-137 promoter. Chromatin immunoprecipitation assays were used to assess direct binding of HMGA1 to the miR-137 promoter. Results: miR-137 and miR-142-3p were predicted to bind FMNL2 based on bioinformatic data. Only the level of miR-137 had a significant inverse correlation with the level of FMNL2 protein in CRC cell lines and tissues. FMNL2 messenger RNA was targeted by miR-137; expression of miR-137 inhibited proliferation and invasion by CRC cells in vitro, and metastasis to liver and intestine by CRC xenografts in nude mice. HMGA1 bound to the promoter of miR-137 and activated its transcription, which reduced levels of FMNL2 in CRC cells. Ectopic expression of miR-137 in CRC cells inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and Akt, which reduced levels of matrix metalloproteinase 2, matrix metalloproteinase 9, and vascular endothelial growth factor; it also reduced invasiveness of CRC cells, inhibiting signaling via phosphatidylinositol-4,5-bisphosphate 3-kinase, Akt, and MAPK. Conclusions: Levels of miR-137 and HMGA1 are reduced, and levels of FMNL2 are increased, in CRC samples compared with adjacent normal mucosa. In CRC cells, miR-137 targets FMNL2 messenger RNA and is regulated by the transcription factor HMGA1. Expression of miR-137 reduces CRC cell invasion in vitro and metastasis of tumor xenografts in mice. FMNL2 appears to activate phosphatidylinositol-4,5-bisphosphate 3-kinase, protein kinase B (Akt), and MAPK signaling pathways. © 2013 AGA Institute.
Nong Y.-q.,Guangdong Women and Children Hospital |
Liu F.-h.,Guangdong Women and Children Hospital |
Chen Y.,Guangdong Women and Children Hospital |
Wang F.,Guangdong Women and Children Hospital
Journal of Assisted Reproduction and Genetics | Year: 2013
Purpose: To determine the role of aquaporin 3 (AQP3) isoform in early embryonic development and protecting embryos subjected to freeze-thawing for assisted reproduction, we investigated the expression and distribution of AQP3 in mouse embryos at different developmental stages before and after vitrification. Methods: Eight-cell embryos, morulae, and blastocysts were obtained from female mice that had been superovulated by controlled ovarian hyperstimulation. Immunofluorescence staining, laser confocal microscopy, and Western blot were used to determine the expression and distribution of AQP3 in preimplantation mouse embryos before and after vitrification. Results: AQP3 was expressed at the 8-cell to blastocyst stage before and after vitrification. The expression and distribution of AQP3 was developmentally regulated at the 8-cell to blastocyst stage. The expression of AQP3 was significantly decreased in 8-cell embryos and early blastocysts after vitrification. However, at the morulae stage, the expression of AQP3 was increased after vitrification. Conclusions: The developmental and vitrification-dependent changes in AQP3 expression and distribution suggest that this transmembrane channel might regulate mouse embryo development and contribute to the protective response during vitrification. © 2013 The Author(s).
Wang Y.,Southern Medical University |
Lin M.,Guangzhou Panyu Central Hospital |
Weng H.,GuangDong Women and Children Hospital |
Wang X.,Southern Medical University |
And 2 more authors.
American Journal of Obstetrics and Gynecology | Year: 2014
Objective Protease-activated receptor 2 plays an important role in the pathogenesis of endometriosis. We studied the effect of ENMD-1068, a protease-activated receptor 2 antagonist, on the development of endometriosis in a noninvasive fluorescent mouse model. Study Design A red fluorescent protein-expressing xenograft model of human endometriosis was created in nude mice. After endometriosis induction, the mice were injected intraperitoneally with either 25 mg/kg or 50 mg/kg ENMD-1068 or with 200 μL of the vehicle control daily for 5 days. The endometriotic lesions that developed in the mice were then counted, measured, and collected. The lesions were assessed for the production of interleukin 6 and monocyte chemotactic protein-1 by enzyme-linked immunosorbent assays and evaluated for the activation of nuclear factor-κB and the expression of vascular endothelial growth factor by immunohistochemical analyses. Cell proliferation and apoptosis were assessed by immunohistochemistry for Ki-67 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, respectively. Results ENMD-1068 dose-dependently inhibited the development of endometriotic lesions (P <.05) without apparent toxicity to various organs of the treated mice. Consistently, ENMD-1068 dose-dependently inhibited the expression of interleukin 6 and nuclear factor-κB (P <.05) and cell proliferation (P <.05) in the lesions, as well as increased the percentage of apoptotic cells (P <.05). ENMD-1068 reduced the levels of monocyte chemotactic protein-1 and vascular endothelial growth factor in the lesions (P <.05), but not in a dose-dependent manner. Conclusion Our study suggests that ENMD-1068 is effective in suppressing the growth of endometriosis, which might be attributed to the drug's antiangiogenic and antiinflammatory activities.
Zhang J.-Y.,Guangdong Women and Children Hospital |
Chen W.-J.,Guangdong Women and Children Hospital
Surgery Today | Year: 2011
Bilateral breast carcinoma accounts for approximately 5% of all patients with breast cancer, while neuroendocrine breast carcinomas comprise less than 5% of invasive breast carcinomas. In addition, most patients with breast neuroendocrine carcinomas are older. Therefore, bilateral primary breast neuroendocrine carcinoma at a young age is extremely rare. We herein report bilateral neuroendocrine carcinoma of the breast in a 29-year-old woman who underwent bilateral lumpectomy with the initial symptom of bilateral nipple discharge. Grossly, the lesions in both breasts were masses with infinite margins. Histologically, this case was consistent with primary neuroendocrine carcinoma arising in bilateral breasts. Cells from both breast tumors were positive for chromogranin A, neuron-specific enolase, synaptophysin, cytokeratin 7, estrogen receptor, and progesterone receptor, and negative for Her2, cytokeratin 34β12, cytokeratin 5/6, smooth muscle actin, p63, S-100 protein, and p53. The Ki67 and NE proliferative indices were below 1%. To the best of our knowledge, this is the first reported case in China of bilateral primary neuroendocrine carcinoma presenting in a young woman. © Springer 2011.
Chen X.,Guangzhou University |
Guo Z.,Guangdong Women and Children Hospital |
Wang P.,Tianjin Medical University |
Xu M.,Guangzhou University
Heart Lung and Circulation | Year: 2014
Background: Doxorubicin (DOX) is a highly effective anti-cancer drug with limited clinical use due to its serious cardiotoxicity. Recent studies reported that erythropoietin (EPO) could exert a cardioprotective effect by non-erythropoietic effects. This study was to investigate fibrosis of DOX-induced cardiotoxicity and determine mechanisms of EPO against extracellular matrix (ECM) remodelling. Methods: Rats were grouped as the control group, the DOX group and the DOX+EPO group. DOX (2.5. mg/kg/dose, six doses for two weeks) was administered to induce cardiotoxicity by intraperitoneal injections in the DOX group and the DOX+EPO group, and EPO (2500U/kg/dose, six doses for two weeks) was administered simultaneously in the DOX+EPO group. Two weeks after the last administration, rats were killed with cardiac tissues used for histological analyses and immunological detections for matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2). Results: Rats treated with DOX showed degenerative changes with cardiac fibrosis. Compared to the control group, the expression of MMP-2 was up-regulated whereas that of TIMP-2 was down-regulated in the DOX group. EPO administration improved cardiac fibrosis, decreased MMP-2 expression, increased TIMP-2 expression and ameliorated imbalance of MMP-2/TIMP-2 ratio. Conclusions: The present study suggests that EPO can exert a cardioprotective effect on DOX-induced cardiotoxicity which may be associated with improving MMP-2/TIMP-2 imbalance. © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).