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Li Z.,Sun Yat Sen University | Li Z.,Guangzhou Medical College | Li Z.,Key Laboratory for Major Obstetric Diseases of Guangdong Province | Wang N.,Sun Yat Sen University | And 6 more authors.
Oncology Reports

This study was designed to investigate the role of protein kinase C (PKC) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in tamoxifen (TAM)-induced apoptosis and drug resistance in human breast cancer cells. Drug-sensitive, or estrogen receptor (ER)-positive human breast carcinoma cells (MCF-7) and the multi-drug-resistant variant (ER-negative) MCF-7/ADR cells were treated with doses of TAM for various periods of time. Cell viability and apoptosis were assessed using cell counting, DNA fragmentation and flow cytometric analysis. We found that TAM administration caused a significant increase in apoptosis of MCF-7 cells but not MCF-7/ADR cells. Western blot analysis revealed enhanced expression of PKCδ but decreased expression of PKCα in ER-positive MCF-7 cells; while ER-negative MCF-7/ADR cells had decreased levels of PKCδ and increased levels of PKCα. Interestingly, we observed that in MCF-7 cells, TAM stimulated apoptosis by promoting rapid activation of PKCδ, antagonizing downstream signaling of ERK phosphorylation; while in MCF-7/ADR cells, TAM upregulated PKCα, which promoted ERK phosphorylation. These results suggest that PKCδ enhances apoptosis in TAM-treated MCF-7 cells by antagonizing ERK phosphorylation; while the PKCα pathway plays an important role in TAM-induced drug resistance by activating ERK signaling in MCF-7/ADR cells. The combination of TAM with PKCα and ERK inhibitors could promote TAM-induced apoptosis in breast cancer cells. Source

Wu Y.,Guangzhou University | Wu Y.,Key Laboratory of Reproductive Medicine of Guangdong Province | Wu Y.,Key Laboratory for Major Obstetric Diseases of Guangdong Province | Wu Y.,Higher Education Institutes | And 4 more authors.

Although the adverse effects of maternal aging on reproductive outcomes have been investigated widely, there is no consensus on the impact of paternal age. Therefore, we investigated the effect of paternal age on reproductive outcomes in a retrospective analysis of 9,991 in vitro fertilization (IVF) cycles performed at the Reproductive Medicine Center of the Third Affiliated Hospital of Guangzhou Medical University (China) between January 2007 and October 2013. Samples were grouped according to maternal age [<30 (3,327 cycles), 30-34 (4,587 cycles), and 35-38 (2,077 cycles)] and then subgrouped according to paternal age (<30, 30-32, 33-35, 36-38, 39-41, and ≥42). The groups did not differ in terms of fertilization rate, numbers of viable and high-quality embryos and miscarriage rate when controlling maternal age (P >0.05). Chi-squared analysis revealed that there were no differences in implantation and pregnancy rates among the different paternal age groups when maternal age was <30 and 35-38 years (P >0.05). However, implantation and pregnancy rates decreased with paternal age in the 31-34 y maternal age group (P <0.05). Our study indicates that paternal age has no impact on fertilization rate, embryo quality at the cleavage stage and miscarriage rate. For the 30-34 y maternal age group, the implantation rate decreased with increased paternal age, with the pregnancy rate in this group being significantly higher in the paternal <30 y and 30-32 y age groups, compared with those in the 36-38 y and 39-41 y groups. Copyright: © 2015 Wu et al. Source

Wu Y.,Guangzhou University | Wu Y.,Key Laboratory of Reproductive Medicine of Guangdong Province | Wu Y.,Key Laboratory for Major Obstetric Diseases of Guangdong Province | Wu Y.,Guangdong Higher Education Institutes | And 5 more authors.

The impact of paternal age on reproduction, especially using assisted reproductive technologies, has not been well studied to date. To investigate the effect of paternal age on reproductive outcomes, here we performed a retrospective analysis of 2,627 intracytoplasmic sperm injection (ICSI) cycles performed at the Reproductive Medicine Center of the Third Affiliated Hospital of Guangzhou Medical University (China) between January 2007 and May 2015. Effect of paternal age on embryo quality [number of fertilized oocytes 2 pronucleus zygotes (2PNs), viable embryos, and high-quality embryos] was analyzed by multiple linear regression. Relationships between paternal age and pregnancy outcomes were analyzed by binary logistic regression. After adjusting for female age, no association between paternal age and the following parameters of embryo quality was observed: number of fertilized oocytes (B = -0.032; 95% CI -0.069-0.005; P = 0.088), number of 2PNs (B = -0.005; 95% CI -0.044-0.034; P = 0.806), and number of viable embryos (B = -0.025; 95% CI -0.052-0.001; P = 0.062). However, paternal age negatively influenced the number of highquality embryos (B = -0.020; 95% CI -0.040-0.000; P = 0.045). Moreover, paternal age had no effect on pregnancy outcomes (OR for a 5-year interval), including the rates of clinical pregnancy (OR 0.919; 95% CI 0.839-1.006; P = 0.067), ongoing pregnancy (OR 0.914; 95% CI 0.833-1.003; P = 0.058), early pregnancy loss (OR 1.019; 95% CI 0.823-1.263; P = 0.861), live births (OR 0.916; 95% CI 0.833-1.007; P = 0.070), and preterm births (OR 1.061; 95% CI 0.898-1.254; P = 0.485). Therefore, increased paternal age negatively influences the number of high-quality embryos, but has no effect on pregnancy outcomes in couples undergoing ICSI cycles. However, more studies including men aged over 60 years with a longer-term follow-up are needed. Copyright © 2016 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source

Huang X.,Sun Yat Sen University | Chen M.,Guangzhou University | Chen M.,Obstetrics and Gynecology Institute of Guangzhou | Chen M.,Key Laboratory for Major Obstetric Diseases of Guangdong Province | And 11 more authors.
Prenatal Diagnosis

Objective: The objective of this study is to assess the performance of noninvasive prenatal testing for trisomies 21 and 18 on the basis of massively parallel sequencing of cell-free DNA from maternal plasma in twin pregnancies. Method: A double-blind study was performed over 12months. A total of 189 pregnant women carrying twins were recruited from seven hospitals. Maternal plasma DNA sequencing was performed to detect trisomies 21 and 18. The fetal karyotype was used as gold standard to estimate the sensitivity and specificity of sequencing-based noninvasive prenatal test. Results: There were nine cases of trisomy 21 and two cases of trisomy 18 confirmed by karyotyping. Plasma DNA sequencing correctly identified nine cases of trisomy 21 and one case of trisomy 18. The discordant case of trisomy 18 was an unusual case of monozygotic twin with discordant fetal karyotype (one normal and the other trisomy 18). The sensitivity and specificity of maternal plasma DNA sequencing for fetal trisomy 21 were both 100% and for fetal trisomy 18 were 50% and 100%, respectively. Conclusion: Our study further supported that sequencing-based noninvasive prenatal testing of trisomy 21 in twin pregnancies could be achieved with a high accuracy, which could effectively avoid almost 95% of invasive prenatal diagnosis procedures. © 2013 John Wiley & Sons, Ltd. Source

Guo L.-Y.,Guangzhou Medical College | Guo L.-Y.,Key Laboratory for Major Obstetric Diseases of Guangdong Province | Guo L.-Y.,Guangzhou Key Laboratory of Reproduction and Genetics | Liu W.-Q.,Guangzhou Medical College | And 11 more authors.
Chinese Journal of Tissue Engineering Research

Background: The studies describing culture of human embryonic stem cells under hypoxic condition mainly focus on the maintenance of pluripotency and differenciation. There are few studies regarding the effects of hypoxia on gene expression in human embryonic stem cells. Objective: To investigate the effects of different oxygen tensions on gene expression profiling of human embryonic stem cells. Methods: Gene expression profiling determined by Human Gene Expression Microarrays and differentially expressed genes were analyzed by gene ontology and pathway analysis in one human embryonic stem cell line (FY-hES-7) following prolonged passage under hypoxia (5%O2) and normoxia (21%O2), respectively. RESULTS AND COCLUSION: 1 840 upregulated genes (more than two folds) and 1676 downregulated genes (more than two folds) were identified in the hypoxic group as compared to the nomorxic group. Gene ontology analysis and pathway analysis showed that gene upregulation in the hypoxic group was associated with cell surface receptor linked signal transduction, immune response, ion transport, metabolic process, cell activation and some pathways such as cytokine-cytokine interaction, immune response, but gene downregulation in the hypoxic group was related to transcription regulation, transcription DNA-dependent regulation, neuronal differentiation, cell morphogenesis, embryonic morphogenesis, embryonic organ and system development and the pathways of embryo development and cancer. The gene expression profiling of human embryonic stem cells in different O2 tensions is variable and the functional analyses of differentially expressed genes in hypoxia are beneficial for human embryonic stem cell culture by keeping stable self-renewal capacity, preventing human embryonic stem cell differentiation and reducing the risk of tumor formation. Source

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