Publications by authors named "Zhi-Ming Cai"

60 Publications

CCL20-CCR6 axis directs sperm-oocyte interaction and its dysregulation correlates/associates with male infertility‡.

Biol Reprod 2020 08;103(3):630-642

Department of Dermatology, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany.

The interaction of sperm with the oocyte is pivotal during the process of mammalian fertilization. The limited numbers of sperm that reach the fallopian tube as well as anatomic restrictions indicate that human sperm-oocyte encounter is not a matter of chance but a directed process. Chemotaxis is the proposed mechanism for re-orientating sperm toward the source of a chemoattractant and hence to the oocyte. Chemokines represent a superfamily of small (8-11 kDa), cytokine-like proteins that have been shown to mediate chemotaxis and tissue-specific homing of leukocytes through binding to specific chemokine receptors such as CCRs. Here we show that CCR6 is abundantly expressed on human sperms and in human testes. Furthermore, radioligand-binding experiments showed that CCL20 bound human sperm in a specific manner. Conversely, granulosa cells of the oocyte-surrounding cumulus complex as well as human oocytes represent an abundant source of the CCR6-specific ligand CCL20. In human ovaries, CCL20 shows a cycle-dependent expression pattern with peak expression in the preovulatory phase and CCL20 protein induces chemotactic responses of human sperm. Neutralization of CCL20 in ovarian follicular fluid significantly impairs sperm migratory responses. Conversely, analyses in infertile men with inflammatory conditions of the reproductive organs demonstrate a significant increase of CCL20/CCR6 expression in testis and ejaculate. Taken together, findings of the present study suggest that CCR6-CCL20 interaction may represent an important factor in directing sperm-oocyte interaction.
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http://dx.doi.org/10.1093/biolre/ioaa072DOI Listing
August 2020

TACC3 transcriptionally upregulates E2F1 to promote cell growth and confer sensitivity to cisplatin in bladder cancer.

Cell Death Dis 2018 01 22;9(2):72. Epub 2018 Jan 22.

State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518039, China.

Accumulating evidence has shown that transforming acidic coiled-coil 3 (TACC3) is deregulated in a broad spectrum of cancers. In the present study, we reported that TACC3 was markedly elevated in bladder cancer, especially in muscle-invasive bladder cancers (MIBCs). The upregulation of TACC3 was positively associated with tumor invasiveness, grade, T stage, and progression in patients with bladder cancer. Furthermore, a Kaplan-Meier survival analysis showed that patients with bladder cancer whose tumors had high TACC3 expression experienced a dismal prognosis compared with patients whose tumors had low TACC3 expression. Functional studies have found that TACC3 is a prerequisite for the development of malignant characteristics of bladder cancer cells, including cell proliferation and invasion. Moreover, TACC3 promoted G1/S transition, which was mediated via activation of the transcription of E2F1, eventually enhancing cell proliferation. Notably, the overexpression of TACC3 or E2F1 indicates a high sensitivity to cisplatin. Taken together, these findings define a tumor-supportive role for TACC3, which may also serve as a prognostic and therapeutic indicator in bladder cancers.
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http://dx.doi.org/10.1038/s41419-017-0112-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833822PMC
January 2018

Effect of continuous positive airway pressure on carotid intima-media thickness in patients with obstructive sleep apnea: A meta-analysis.

PLoS One 2017 1;12(9):e0184293. Epub 2017 Sep 1.

From Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Xiangcheng District, Zhangzhou, Fujian Province, People's Republic of China.

Objective: Obstructive sleep apnea (OSA) is associated with increased carotid intima-media thickness (IMT), an early marker of atherosclerosis. Continuous positive airway pressure (CPAP) is the first-line treatment for OSA. A meta-analysis was performed to determine whether CPAP therapy could decrease carotid IMT.

Methods: The PubMed, Embase, Web of Science, and Cochrane library were searched before March, 2017. Weighted mean difference (WMD) was calculated to estimate the treatment effects of pre and post-CPAP therapy. Seven studies were examined and the meta-analysis was performed using STATA 12.0.

Results: There was no change of carotid IMT before and after CPAP treatment in OSA patients (WMD = 0.052, 95% confidence interval (CI) = -0.002 to 0.105, z = 1.90, p = 0.057). Meanwhile, meta-analysis of the two RCTs showed that carotid IMT was not changed in CPAP group when compared with control group (WMD = 0.002 95% CI = -0.125 to 0.129, z = 0.03, p = 0.976). Subgroup analyses indicated that carotid IMT was significantly decreased after CPAP use in more severe OSA patients (AHI≥50) (WMD = 0.073, 95% CI = 0.022 to 0.124, z = 2.80, p = 0.005) and patients with therapeutic duration ≥6 months (WMD = 0.121, 95% CI = 0.019 to 0.223, z = 2.32, p = 0.021).

Conclusions: CPAP had no impact on carotid IMT in OSA patients. However, carotid IMT was significantly decreased after CPAP treatment in more severe OSA patients and patients with longer CPAP usage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184293PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580911PMC
October 2017

EGCG inhibited bladder cancer SW780 cell proliferation and migration both in vitro and in vivo via down-regulation of NF-κB and MMP-9.

J Nutr Biochem 2017 03 20;41:56-64. Epub 2016 Dec 20.

State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China. Electronic address:

Epigallocatechin-3-gallate (EGCG), the bioactive polyphenol in green tea, has been demonstrated to have various biological activities. Our study aims to investigate the antiproliferation and antimigration effects of EGCG against bladder cancer SW780 cells both in vitro and in vivo. Our results showed that treatment of EGCG resulted in significant inhibition of cell proliferation by induction of apoptosis, without obvious toxicity to normal bladder epithelium SV-HUC-1 cells. EGCG also inhibited SW780 cell migration and invasion at 25-100 μM. Western blot confirmed that EGCG induced apoptosis in SW780 cells by activation of caspases-8, -9 and -3, Bax, Bcl-2 and PARP. Besides, animal study demonstrated that EGCG [100 mg/kg, intraperitoneal (i.p.) injection daily for 3 weeks] decreased the tumor volume significantly in mice bearing SW780 tumors, as well as the tumor weight (decreased by 68.4%). In addition, EGCG down-regulated the expression of nuclear factor-kappa B (NF-κB) and matrix metalloproteinase (MMP)-9 in both protein and mRNA level in tumor and SW780 cells. When NF-κB was inhibited, EGCG showed no obvious effect in cell proliferation and migration. In conclusion, our study demonstrated that EGCG was effective in inhibition SW780 cell proliferation and migration, and presented first evidence that EGCG inhibited SW780 tumor growth by down-regulation of NF-κB and MMP-9.
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http://dx.doi.org/10.1016/j.jnutbio.2016.12.004DOI Listing
March 2017

Expression profile of / in spermatogenesis and transitional cell carcinoma of the bladder.

Oncol Lett 2016 Nov 21;12(5):3731-3738. Epub 2016 Sep 21.

Department of Science and Education, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518035, P.R. China.

The majority of bladder cancer-associated mortalities are due to transitional cell carcinoma (TCC), which is the most prevalent and chemoresistant malignancy of the bladder. Sperm acrosome associated 5 (SPACA5)/Spaca5 is a sperm acrosome-associated, c-type lysozyme-like protein that has been recently identified, and has been designated as an attractive candidate antigen for cancer testis. In the present study, the expression profile of / was analyzed in spermatogenesis and TCC of the bladder using diverse molecular and cellular biology methods. Using reverse transcription-polymerase chain reaction (RT-PCR) to analyze the multi-tissue distribution and temporal expression of /, the / gene was determined to be generally not expressed in normal tissue, with the exception of the testis, and it could be detected at a low level on day 20 after birth in mouse testes and at a higher level on day 28. Immunohistochemistry staining revealed that the SPACA5/Spaca5 protein was exclusively observed in the elongated spermatid of the normal testes, and was ectopically expressed in the cytoplasm of TCC, while it was not expressed in normal bladder tissues. The frequency of messenger RNA was detected in 45% of TCC (9/20) by RT-quantitative PCR. Furthermore, SPACA5 protein was more frequently detected in high-grade than in low-grade tumors (61.54 vs. 30.00%, P=0.035). Accordingly, high SPACA5 staining scores were observed to be significantly associated with high-grade tumors (n=65, R=0.279, P=0.027). Collectively, our findings indicated that / may be important in male spermatogenesis and may be used as a potential target for specific immunotherapy in patients suffering from TCC.
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http://dx.doi.org/10.3892/ol.2016.5164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104159PMC
November 2016

[Testicular malignant Leydig cell tumor: A case report].

Zhonghua Nan Ke Xue 2016 May;22(5):442-5

Objective: To investigate the clinicopathological features of testicular malignant Leydig cell tumor (TMLCT) and improve the non-invasive diagnosis of the disease.

Methods: We retrospectively analyzed the clinicopathological data on a case of TMLCT, detected the circulating tumor cells (CTC) in the peripheral venous blood, and reviewed the related literature.

Results: The patient, a 47-year-old male, underwent radical orchidoepididymectomy under general anesthesia. Postoperative pathology confirmed the lesion to be TMLCT, which was mainly composed of Leydig cells and suspected with vessel carcinoma embolus. Immunohistochemistry showed the tumor cells to be positive for α-inhibin, Ki67, CD30, vimentin, EMA, and PLAP, but negative for CK, CK7, S100, CD10, SMA, Des, AFP, hCG, CEA, CK19, CD117, Oct-4, LCA, CD20, Pax-5, CD3, and CD43. Two CTCs were detected in the peripheral venous blood. The patient received 3 courses of chemotherapy for retroperitoneal multiple lymph nodes metastasis post-operatively. Subsequent CT imaging manifested no obvious reduction of the retroperitoneal lymph nodes and consequently the patient again underwent retroperitoneal lymphadenectomy and cryoablation. At 8 months after treatment, CT examination revealed notably enlarged retroperitoneal lymph nodes with the right adrenal gland evidently invaded.

Conclusion: TMLCT is an extremely rare sex-gonad stromal tumor with high malignancy and poor prognosis, and CTCs may be used for its early diagnosis and prognostic prediction.
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May 2016

Effect of positive airway pressure on glomerular filtration rate in patients with sleep-disordered breathing: a meta-analysis.

Sleep Breath 2017 Mar 3;21(1):53-59. Epub 2016 Jun 3.

Department of Respiratory Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, No 59, Shenglixi road, Xiangcheng district, Zhangzhou, Fujian province, 363000, People's Republic of China.

Objective: Sleep-disordered breathing (SDB) has been suggested to be associated with chronic kidney disease (CKD). Positive airway pressure (PAP) is an effective treatment for SDB, but the impact of PAP therapy on glomerular filtration rate (GFR) in patients with SDB remains unclear. The present meta-analysis was performed to determine whether PAP therapy could increase GFR.

Design: A systematic search of PubMed, Embase, Web of Science, and Cochrane library was performed for literature published up to January 2016. Standardized mean difference (SMD) was calculated to estimate the treatment effects of pre- and post-PAP therapy.

Results: A total of eight studies with 240 patients were pooled into a meta-analysis. The meta-analysis showed that there was no change of GFR before and after PAP treatment in SDB patients (SMD = 0.010, 95 % confidence interval (CI) = -0.331 to 0.350, z = 0.06, p = 0.956), Subgroup analyses indicated that GFR was significantly increased after PAP treatment in elder patients (≥55 years) (SMD = -0.283, 95 % CI = -0.518 to -0.047, z = 2.35, p = 0.019) and patients with therapeutic duration ≥ 3 months (SMD = -0.276, 95 % CI = -0.522 to -0.031, z = 2.20, p = 0.027).

Conclusion: The present meta-analysis suggested that PAP treatment had no impact on GFR in SDB patients. However, longer PAP usage for SDB patients significantly improved GFR. In elder SDB subjects, PAP was also associated with a statistically significant increase in GFR.
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http://dx.doi.org/10.1007/s11325-016-1364-6DOI Listing
March 2017

Hedyotis diffusa plus Scutellaria barbata Induce Bladder Cancer Cell Apoptosis by Inhibiting Akt Signaling Pathway through Downregulating miR-155 Expression.

Evid Based Complement Alternat Med 2016 17;2016:9174903. Epub 2016 Feb 17.

The Affiliated Clinical College Shenzhen Second People's Hospital, Anhui Medical University, Hefei 230032, China; The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518035, China.

Traditional Chinese medicine is increasingly used to treat cancer. Our clinical experiences identify Hedyotis diffusa plus Scutellaria barbata as the most common herb-pair (couplet medicinal) used for the core treatment of bladder cancer. This study aims to investigate the antitumor effect of the herb-pair in bladder cancer cells. The results show that Hedyotis diffusa plus Scutellaria barbata inhibited bladder cancer cell growth and clone formation in a dose-dependent and time-dependent manner. It also induced cell apoptosis through decreasing Akt activation and reducing the expression of antiapoptotic proteins Bcl-2 and Mcl-1. Further experiments showed that miR-155 was reduced by the herb-pair and miRNA-155 inhibitor induced cell apoptosis and suppressed Akt activation. Overexpression of miR-155 reversed herb-pair induced cell apoptosis through activating Akt pathway in both bladder cancer cell lines. The findings reveal that Hedyotis diffusa plus Scutellaria barbata reduce Akt activation through reducing miR-155 expression, resulting in cell apoptosis. It demonstrated the potential mechanism of Hedyotis diffusa plus Scutellaria barbata for the core treatment of bladder cancer.
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http://dx.doi.org/10.1155/2016/9174903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773537PMC
March 2016

Reprogrammed CRISPR-Cas9 targeting the conserved regions of HPV6/11 E7 genes inhibits proliferation and induces apoptosis in E7-transformed keratinocytes.

Asian J Androl 2016 May-Jun;18(3):475-9

Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei; Key Laboratory of Dermatology, Ministry of Education, State Key Laboratory of Dermatology Incubation Center, Department of Dermatology, Anhui Medical University, Hefei, China.

The persistence infection of low-risk type (type 6 or type 11) of human papillomavirus (HPV) is the main cause of genital warts. Given the high rate of recurrence after treatment, the use of a new molecular agent is certain to be of value. The aim of this study was to achieve targeted inactivation of viral E 7 gene in keratinocytes using the reprogrammed clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system. To accomplish this, a universal CRISPR-Cas9 system for targeting both HPV6/11 E 7 genes was constructed by using a dual guide RNA vector. After transfection of the vector into E 7-transformed keratinocytes, the expression level of E 7 protein was measured using western-blot analysis and the sequence of the E 7 gene was determined using Sanger sequencing. Cell proliferation was analyzed by CCK-8 assay, and cell apoptosis was evaluated by Hoechst 33258 staining, flow cytometry analysis and ELISA assay. The results indicated that both HPV6/11 E 7 genes can be inactivated by the single CRISPR-Cas9 system. Furthermore, silencing of E 7 led to inhibition of cell proliferation and induction of apoptosis in E 7-transformed keratinocytes but not in normal keratinocytes. Our data suggested that the reprogrammed CRISPR-Cas9 system has the potential for the development of an adjuvant therapy for genital warts.
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http://dx.doi.org/10.4103/1008-682X.157399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854108PMC
January 2017

Meta-Analysis of the Association between H63D and C282Y Polymorphisms in HFE and Cancer Risk.

Asian Pac J Cancer Prev 2015 ;16(11):4633-9

Shenzhen Second People's Hospital, clinical medicine college of Anhui Medical University, Shenzhen Guangdong, China E-mail :

Background: Previous studies suggested that the H63D and C282Y polymorphisms in the HFE genes were susceptible to many cancer types, nevertheless, the present results were inconclusive. Thus, the present study was aimed to evaluate the association between the HFE polymorphisms (H63D and C282Y) and cancer risk via meta-analysis.

Materials And Methods: We retrieved PubMed, Google Scholar, Embase and Web of Science databases for all eligible studies up to April 1, 2015. All the statistical analysis was conducted by STATA 12.0.

Results: Finally, a total of 20 publications including 24 case-control studies, comprising 6,524 cases and 31,080 controls for HFE-C282Y polymorphism and 19 publications including 21 case control studies, comprising 5,648 cases and 14,257 controls for HFE-H63D polymorphism were enrolled in our analysis. An increased risk for overall cancer risk was identified in HFE-H63D polymorphism under allele contrast (D vs H: OR=1.153; 95%CI=1.031- 1.289, Pheterogeneity=0.002), homozygotes vs wide type (DD vs HH: OR=1.449; 95%CI=1.182-1.777, Pheterogeneity=0.391), dominant model (DD+HD vs HH: OR=1.145; 95%CI=1.007-1.301, Pheterogeneity=0.002) and recessive model (DD vs HD+HH: OR=1.416 ; 95%CI=1.156-1.735, Pheterogeneity=0.549), as well as HFE- C282Y under homozygotes vs wide type (YY vs CC: OR=1.428, 95%CI=1.017-2.006, Pheterogeneity=0.220). In addition, in the stratified analysis by cancer type, an increased risk was identified in hepatocellular carcinoma and breast cancer in C282Y polymorphism, as well as pancreatic cancer in H63D polymorphism, whereas a decreased risk of colorectal cancer was identified in C282Y polymorphism.

Conclusions: Present study suggested that H63D and C282Y polymorphisms associated with an increased risk of overall cancer. Nevertheless, well- designed study with large sample size will be continued on this issue of interest.
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http://dx.doi.org/10.7314/apjcp.2015.16.11.4633DOI Listing
April 2016

Paraoxonase 1 (PON1) Q192R Gene Polymorphism and Cancer Risk: A Meta-Analysis Based on 30 Publications.

Asian Pac J Cancer Prev 2015 ;16(10):4457-63

Shenzhen Second People's Hospital, clinical medicine college of Anhui Medical University, Shenzhen Guangdong, China E-mail :

Common genetic variation Q192R in the paraoxonase 1 (PON1) gene has been considered to be implicated in the development of many cancers. Nevertheless, results from the related studies were inconsistent. To elucidate the association, we performed a meta-analysis for 8,112 cases and 10,037 controls from 32 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association by STATA 12.0 software. Overall, we revealed that the PON1-192R allele was associated with a reduced risk of the overall cancers. Moreover, in the stratified analysis by cancer types (breast cancer, prostate cancer, brain cancer etc.), the results showed that PON1-192R allele was associated with a decreased risk in breast cancer (R vs Q: OR=0.605, 95% CI=0.378-0.967, Pheterogeneity=0.000; RR vs QQ: OR=0.494, 95% CI=0.275-0.888, Pheterogeneity=0.002; RQ vs QQ: OR=0.465, 95% CI=0.259-0.835, Pheterogeneity=0.000; and RR+RQ vs QQ: OR=0.485, 95% CI=0.274-0.857, Pheterogeneity=0.000), and associated with prostate cancer in homozygote (RR vs QQ: OR=0.475, 95% CI=0.251- 0.897, Pheterogeneity=0.001) and recessive models (RR vs RQ+QQ: OR=0.379, 95% CI=0.169-0.853, Pheterogeneity=0.000), while an increased risk was identified in lymphoma (R vs Q: OR=1.537, 95% CI=1.246-1.896, Pheterogeneity=0.944; RR vs QQ: OR=2.987, 95% CI=1.861-4.795, Pheterogeneity=0.350; RR+RQ vs QQ: OR=1.354, 95% CI=1.021-1.796, Pheterogeneity=0.824; and RR vs RQ+QQ: OR=2.934, 95% CI=1.869-4.605, Pheterogeneity=0.433), and an increased risk in prostate cancer under heterozygote comparison (RQ vs QQ: OR=1.782, 95% CI=1.077-2.950, Pheterogeneity=0.000) and dominant models (RR+RQ vs QQ: OR=1.281, 95% CI=1.044-1.573, Pheterogeneity=0.056). When subgroup analysis that performed by the control source (hospital based or population based), a decreased risk of the overall cancers was revealed by homozygote (RR vs QQ: OR=0.601, 95% CI=0.366-0.987, Pheterogeneity=0.000) and dominant models (RR vs RQ+QQ: OR=0.611, 95% CI=0.384-0.973, Pheterogeneity=0.000) in hospital based group. Stratifying by ethnicity, a significantly reduced risk of the overall cancers under allele contrast model (R vs Q: OR=0.788, 95% CI=0.626-0.993, Pheterogeneity=0.000) was uncovered in Caucasian. In summary, these findings suggested that PON1 Q192R polymorphism was associated with a reduced risk of the overall cancers, nevertheless, it might increase cancer susceptibility of prostate and lymphoma risk. Large well-designed epidemiological studies will be continued on this issue of interest.
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http://dx.doi.org/10.7314/apjcp.2015.16.10.4457DOI Listing
February 2016

[Updated genomics of testicular germ cell tumor].

Zhonghua Nan Ke Xue 2015 Apr;21(4):363-70

Testicular germ cell tumor (TGCT) is a most common testicular malignancy with an increasing incidence, and its pathogenesis and mechanisms are not yet clear. The next generation sequencing has become the main tool to uncover the underlying mechanisms of TGCT. The differential gene expressions, gene mutation, predisposing gene-dominated signaling pathways, and changes of the relevant genes in the sex chromosome are largely involved in the occurrence and development of TGCT. Studies on the genomics of TGCT contribute a lot to identifying the pivotal pathogenic genes and paving a theoretical ground for the early screening and targeted therapy of TGCT. This paper summarizes the advances in the studies of the genomics of TGCT so as to reveal thetmechanisms of the disease at the genetic level.
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April 2015

Synthetic miRNA sponges driven by mutant hTERT promoter selectively inhibit the progression of bladder cancer.

Tumour Biol 2015 Jul 10;36(7):5157-63. Epub 2015 Feb 10.

Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, Shenzhen, 518039, Guangdong, People's Republic of China.

The mutant promoter of human telomerase reverse transcriptase (hTERT) shows high transcriptional activity in bladder cancer cells. Some up-regulated microRNAs (miRNAs) are reported as oncogenic factors in bladder cancer. Previous studies report that miRNAs can be inhibited by base-pairing interactions. The purpose of this study is to construct a synthetic device driven by mutant hTERT promoter to suppress four up-regulated miRNAs and to verify its effects on phenotypes of bladder cancer cells and human normal cells. Tandem bulged miRNA binding sites targeting oncogenic miRNAs were inserted into the 3' untranslated region (3' UTR) of mutant hTERT promoter-driven Renilla luciferase gene to construct a synthetic tumor-specific device, miRNA sponges. A negative control was generated by using tandem repeated sequences without targeting any known miRNA. Bladder cancer cells (T24, 5637, UM-UC-3) and human fiber cells (HFC) were transfected with devices. Various functional assays were used to detect the effects of this device. The activity of the mutant hTERT promoter detected by luciferase assay was about three times as large as the wild-type hTERT promoter in bladder cancer cells, while it could not be measured in HFC. Other assays indicated that the synthetic device can significantly inhibit cell growth, decrease motility, and induce apoptosis in bladder cancer cells but not in HFC. A synthetic biology platform is employed to construct tumor-specific miRNA sponges that can be used to target oncogenic miRNAs to inhibit the progression of bladder cancer cells without affecting normal cells.
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http://dx.doi.org/10.1007/s13277-015-3169-9DOI Listing
July 2015

[UBE2B gene and male infertility: an update].

Zhonghua Nan Ke Xue 2014 Apr;20(4):367-71

Male infertility is a worldwide problem, and about 15% of the cases are associated with spermatogenesis-related gene mutation. The mammalian gene UBE2B is the homolog of the RAD6 gene of yeast, belonging to the ubiquitin proteasome system and playing an important role in spermatogenesis. Mice lacking the UBE2B gene are infertile, with reduced sperm motility, increased morphologically abnormal sperm, and inhibited meiosis of spermatogonia. Accumulated evidence shows that UBE2B gene mutants and single nucleotide polymorphisms are associated with male infertility. This article reviews the relation between the UBE2B gene and male infertility, offering some theoretical evidence for the diagnosis and treatment of male infertility.
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April 2014

Microfluidic chip capillary electrophoresis coupled with electrochemiluminescence for enantioseparation of racemic drugs using central composite design optimization.

Electrophoresis 2013 Nov 3;34(20-21):2962-9. Epub 2013 Oct 3.

Shenzhen Second People's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, P. R. China; Department of Chemistry, The University of Hong Kong, Hong Kong, P. R. China.

Optimization based on central composite design (CCD) for enantioseparation of anisodamine (AN), atenolol (AT), and metoprolol (ME) in human urine was developed using a microfluidic chip-CE device. Coupling the flexible and wide working range of microfluidic chip-CE device to CCD for chiral separation of AN, AT, and ME in human urine, a total of 15 experiments is needed for the optimization procedure as compared to 75 experiments using the normal one variable at a time optimization. The optimum conditions obtained are found to be more robust as shown by the curvature effects of the interaction factors. The developed microfluidic chip-CE-ECL system with adjustable dilution ratios has been validated by satisfactory recoveries (89.5-99% for six enanotiomers) in urine sample analysis. The working range (0.3-600 μM), repeatability (3.1-4.9% RSD for peak height and 4.0-5.2% RSD for peak area), and detection limit (0.3-0.6 μM) of the method developed are found to meet the requirements for bedside monitoring of AN, AT, and ME in patients under critical conditions. In summary, the hyphenation of CCD with the microfluidic chip-CE device is shown to offer a rapid means for optimizing the working conditions on simultaneous separation of three racemic drugs using the microfluidic chip-CE device developed.
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http://dx.doi.org/10.1002/elps.201300238DOI Listing
November 2013

The Wilms tumor gene, Wt1, is critical for mouse spermatogenesis via regulation of sertoli cell polarity and is associated with non-obstructive azoospermia in humans.

PLoS Genet 2013 1;9(8):e1003645. Epub 2013 Aug 1.

State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Azoospermia is one of the major reproductive disorders which cause male infertility in humans; however, the etiology of this disease is largely unknown. In the present study, six missense mutations of WT1 gene were detected in 529 human patients with non-obstructive azoospermia (NOA), indicating a strong association between WT1 mutation and NOA. The Wilms tumor gene, Wt1, is specifically expressed in Sertoli cells (SCs) which support spermatogenesis. To examine the functions of this gene in spermatogenesis, Wt1 was deleted in adult testis using Wt1(flox) and Cre-ER(TM) mice strains. We found that inactivation of Wt1 resulted in massive germ cell death and only SCs were present in most of the seminiferous tubules which was very similar to NOA in humans. In investigating the potential mechanism for this, histological studies revealed that the blood-testis barrier (BTB) was disrupted in Wt1 deficient testes. In vitro studies demonstrated that Wt1 was essential for cell polarity maintenance in SCs. Further studies found that the expression of cell polarity associated genes (Par6b and E-cadherin) and Wnt signaling genes (Wnt4, Wnt11) were downregulated in Wt1 deficient SCs, and that the expression of Par6b and E-cadherin was regulated by Wnt4. Our findings suggest that Wt1 is important in spermatogenesis by regulating the polarity of SCs via Wnt signaling pathway and that WT1 mutation is one of the genetic causes of NOA in humans.
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http://dx.doi.org/10.1371/journal.pgen.1003645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731222PMC
March 2014

Downregulation of CFTR promotes epithelial-to-mesenchymal transition and is associated with poor prognosis of breast cancer.

Biochim Biophys Acta 2013 Dec 2;1833(12):2961-2969. Epub 2013 Aug 2.

Epithelial Cell Biology Research Center, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong; Key Laboratory for Regenerative Medicine, Ji Nan University-The Chinese University of Hong Kong, Ministry of Education of The People's Republic of China, China; Sichuan University-The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Chengdu, China. Electronic address:

The epithelial-to-mesenchymal transition (EMT), a process involving the breakdown of cell-cell junctions and loss of epithelial polarity, is closely related to cancer development and metastatic progression. While the cystic fibrosis transmembrane conductance regulator (CFTR), a Cl(-) and HCO3(-) conducting anion channel expressed in a wide variety of epithelial cells, has been implicated in the regulation of epithelial polarity, the exact role of CFTR in the pathogenesis of cancer and its possible involvement in EMT process have not been elucidated. Here we report that interfering with CFTR function either by its specific inhibitor or lentiviral miRNA-mediated knockdown mimics TGF-β1-induced EMT and enhances cell migration and invasion in MCF-7. Ectopic overexpression of CFTR in a highly metastatic MDA-231 breast cancer cell line downregulates EMT markers and suppresses cell invasion and migration in vitro, as well as metastasis in vivo. The EMT-suppressing effect of CFTR is found to be associated with its ability to inhibit NFκB targeting urokinase-type plasminogen activator (uPA), known to be involved in the regulation of EMT. More importantly, CFTR expression is found significantly downregulated in primary human breast cancer samples, and is closely associated with poor prognosis in different cohorts of breast cancer patients. Taken together, the present study has demonstrated a previously undefined role of CFTR as an EMT suppressor and its potential as a prognostic indicator in breast cancer.
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http://dx.doi.org/10.1016/j.bbamcr.2013.07.021DOI Listing
December 2013

Overexpression of cyclooxygenase-1 correlates with poor prognosis in renal cell carcinoma.

Asian Pac J Cancer Prev 2013 ;14(6):3729-34

Department of Urology, Peking University Shenzhen Hospital, Shenzhen, China.

The aim of this study was to evaluate expression of COX-1 in renal cell carcinoma (RCC) and its prognostic value. mRNA of COX-1 was detected in 42 paired RCC and adjacent normal tissues with quantitative real- time polymerase chain reaction (qRT-PCR). Expression of COX-1 was also evaluated in 196 RCC sections and 91 adjacent normal tissues with immunohistochemistry. Statistical analysis was performed to assess COX-1 expression in RCC and its prognostic significance. The results of qRT-PCR showed mRNA levels of COX-1 in RCC tissues to be significantly higher than that in adjacent normal tissues (p < 0.001). Immunohistochemical assays also revealed COX-1 to be overexpressed in RCC tissues (p < 0.001). Statistical analysis demonstrated high expression of COX-1 was correlated with tumour size (p = 0.002), pathological stage (p = 0.003), TNM stage (p = 0.003, 0.007, 0.027, respectively), and tumour recurrence (p < 0.001). Survival analysis indicated patients with high expression of COX-1 had shorter survival time (p < 0.001), and COX-1 was an independent predictor. This is the first study to reveal overexpression of COX-1 in RRC and point to use as a prognostic marker in affected patients.
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http://dx.doi.org/10.7314/apjcp.2013.14.6.3729DOI Listing
February 2014

Renal plasmacytoma: Report of a rare case and review of the literature.

Oncol Lett 2013 Jun 3;5(6):1839-1843. Epub 2013 Apr 3.

State Key Laboratory of Oncology in Southern China, Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060;

Renal plasmacytoma is extremely rare, presenting diagnostic challenges due to its unusual location and non-specific or absent symptoms. To the best of our knowledge, only 24 cases of renal plasmacytoma have been reported in the literature. The present study reports a case of primary renal plasmacytoma in a 46-year-old female patient. Computed tomography (CT) revealed that the mass was located in the lower pole of the left kidney and metastasis was detected in an enlarged para-aortic lymph node. Following careful preparation, a partial nephrectomy was performed and the retroperitoneal lymph node was resected. A pathological examination revealed a renal parenchyma with lymph node involvement; this was confirmed by immunohistochemistry and nested polymerase chain reaction (PCR). Consequently, a diagnosis of a renal extramedullary plasmacytoma (EMP) was proposed. Following this unexpected diagnosis, various examinations were performed, but there was no evidence of systemic plasma cell disease. The patient refused further therapy, including external beam radiotherapy and chemotherapy. Abdominal CT was performed three months post-surgery and did not reveal any relapse. The patient remains disease-free at nine months post-surgery. The current study also presents a review of the literature. Although the general prognosis and outcome of EMP is good, a follow-up examination is recommended due to the possibility of relapse or progression to plasma cell neoplasm (PCN).
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http://dx.doi.org/10.3892/ol.2013.1282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700893PMC
June 2013

Clinical outcomes in patients with stage I non-seminomatous germ cell cancer.

Asian J Androl 2013 Jul 20;15(4):558-63. Epub 2013 May 20.

Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518036, China.

This study assesses the long-term outcomes in Han Chinese patients with clinical stage I non-seminomatous germ cell testicular cancer (CSI NSGCT) treated with surveillance, retroperitoneal lymph node dissection (RPLND) and adjuvant chemotherapy. We retrospectively evaluated 89 patients with a mean age of 26.5 years. After orchiectomy, 37 patients were treated with surveillance, 34 underwent RPLND and 18 were managed with chemotherapy. The overall survival rate, the recurrence-free survival rate and the risk factors were evaluated. The median follow-up length was 92 months (range: 6-149 months). Thirteen of the 89 patients (14.6%) had relapses, and one died by the evaluation date. The overall survival rate was 98.9%. The cumulative 4-year recurrence-free rates were 80.2%, 92.0% and 100% for the surveillance, RPLND and chemotherapy groups, respectively. The disease-free period tended to be briefer in patients with a history of cryptorchidism and those with stage Is. Therefore, surveillance, RPLND and adjuvant chemotherapy might be reliable strategies in compliant patients with CSI NSGCT. Surveillance should be recommended for patients with the lowest recurrence rate, especially those without lymphovascular invasion. This study might aid the establishment of a standard therapy for CSI NSGCT in China.
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http://dx.doi.org/10.1038/aja.2013.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739228PMC
July 2013

[Tumor suppressor role of chromatin-remodeling factor ARID1A].

Yi Chuan 2013 Mar;35(3):255-61

Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China.

The mammalian SWI/SNF complex is one of ATP-dependent chromatin-remodeling complexes, which plays important roles in cell proliferation, differentiation, development and tumor suppression. ARID1A (AT-rich interactive domain-containing protein 1A) is a large subunit of SWI/SNF complex, and also an ARID family member with non- sequence-specific DNA binding activity. ARID1A is a tumor suppressor gene which is frequently mutated in many cancers, such as ovarian, bladder and gastric cancers. ARID1A can suppress cell proliferation through the up-regulation of p21 and the down-regulation of E2F-responsive genes. These findings on ARID1A and its role of tumor suppression contribute to understanding the mechanism of cancer development and developing new therapy for cancer.It is introduced in the review that ARID1A basic characteristic, related to cancer development, and biological role for full understanding of ARID1A.
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http://dx.doi.org/10.3724/sp.j.1005.2013.00255DOI Listing
March 2013

Elevated serum cystatin C in severe OSA younger men without complications.

Sleep Breath 2013 Mar 16;17(1):235-41. Epub 2012 Mar 16.

Department of Respiratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.

Purpose: Serum cystatin C is a promising new biomarker of glomerular filtration rate and cardiovascular events, but few studies focused on serum cystatin C levels in obstructive sleep apnea (OSA) patients. The aim of our study was to evaluate the association between serum cystatin C and OSA in younger men (≤40 years old of age) without complications.

Methods: We prospectively recruited consecutive participants without comorbidities who underwent polysomnography. Fasting blood samples were obtained from all subjects for biological profile measurements. Statistical analysis was used to evaluate the relationship between serum cystatin C and other parameters.

Results: The population consisted of 98 subjects (mean age = 32.5 years, mean body mass index = 27.93 kg/m(2)) that were divided according to polysomnographic finding into control group (n = 23), mild (n = 15), moderate (n = 24), and severe (n = 36) OSA group. Compared with the control group, patients with severe OSA were significantly heavier (body mass index, 29.69 ± 3.81 vs. 26.42 ± 3.10) and presented significantly higher levels of high sensitive C-reactive protein (hsCRP) (1.10 ± 0.28 vs. 0.88 ± 0.20 mg/l) and serum cystatin C (0.87 ± 0.12 vs. 0.74 ± 0.10 mg/l) (p < 0.05 for all comparisons). Cystatin C was correlated with Apnea Hypopnea Index (AHI), Oxygen Desaturation Index, hsCRP, creatinine, and estimated glomerular filtration rate (r = 0.319, 0.279, 0.321, 0.233, -0.241, p = 0.001, 0.005, 0.001, 0.021, 0.017, respectively). After adjustment for confounding factors, AHI was significantly and positively associated with serum cystatin C levels (β = 0.284, p = 0.007).

Conclusions: Our finding indicated that serum cystatin C was associated with the severity of OSA in younger men. Further study is needed to find out whether OSA patients with increased serum cystatin C levels are prone to subclinical cardiovascular and renal diseases.
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http://dx.doi.org/10.1007/s11325-012-0678-2DOI Listing
March 2013

Effect of all-trans-retinoic acid on the expression of primordial germ cell differentiation-associated genes in mESC-derived EBs.

Cell Biol Int 2012 May;36(5):491-5

Guangdong Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, The Institute of Urology, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, Peoples Republic of China.

atRA (all-trans-retinoic acid) is known to induce the differentiation of mESCs (mouse embryonic stem cells) into PGCs (primordial germ cells) in vitro. However, it is not clear as to what changes occur in PGC differentiation-associated genes or what mechanisms are involved when EBs (embryoid bodies) derived from mESCs are induced by atRA. EBs derived from mESCs were treated with 1, 2 or 5 μM atRA for 16 h, 2 days or 5 days. Real-time PCR and Western blot analysis were performed to detect the relative levels of PGC differentiation-associated genes (Lin28, Blimp1, Stra8 and Mvh) and the corresponding proteins respectively. Immunofluorescence was used to detect the protein location and distribution in EBs. The expression characteristics of genes could be divided into three categories: rapidly reached the peak value in 16 h and then decreased (Stra8, Lin28), initially low and then increased to reach the peak value in 5 days (Mvh) and relatively unchanged (Blimp1). A low level of Lin28 was expressed in EBs treated with atRA for 2 days or 5 days. The variation in the level of Lin28 mRNA did not influence the change in the level of Blimp1 mRNA. The changes in Stra8/Lin28 were consistent with the corresponding changes in the levels of their respective mRNAs, but the changes for Mvh/Blimp1 were not consistent with the corresponding changes in the levels of their respective mRNAs. Blimp1 expression may be independent of the effect of atRA on PGC differentiation. atRA may promote the start of a period in which there is a low level of Lin28 expression during PGC differentiation.
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http://dx.doi.org/10.1042/CBI20110423DOI Listing
May 2012

[Mouse-induced pluripotent stem cells have the potential to differentiate into induced primordial germ cells].

Zhonghua Nan Ke Xue 2011 Nov;17(11):966-72

Key Laboratory of Male Reproduction and Genetics of Guangdong Province, Shenzhen Hospital of Peking University, Shenzhen, Guangdong 518036, China.

Objective: To investigate whether mouse-induced pluripotent stem (iPS) cell line IP14D-1 has the potential to differentiate into induced primordial germ cells (iPGCs), and to explore the changes in the expression of iPGCs-differentiation associated genes and their possible mechanisms.

Methods: Undifferentiated IP14D-1 was cultured to proliferate and then differentiated to form 4-, 7- and 9-day-old induced embryoid bodies (iEBs) in vitro, respectively. RT-PCR and immunofluorescence were used to detect the expressions of Lin28, Blimpl, Stra8 and Mvh, as well as the localization of the corresponding protein in iEBs.

Results: The expression of Blimpl was higher than that of Lin28 in the undifferentiated IP14D-1 and mouse embryonic stem cells (mESCs). Mvh and Stra8 as well as mESCs and EBs were also expressed in IP14D-1 and iEBs, but with no significant differences. The expression of Lin28 was gradually increased in the IP14D-1-derived iEBs from 4 to 7 days, but decreased at 9 days, and the expression of Blimp1 was gradually reduced with the prolonged growing time of iEBs.

Conclusion: A stable system was established for the culture and differentiation of IP14D-1 and IP14D-1-derived iEBs. The expressions of Lin28, Blimp1, Mvh and Stra8 were not significantly different between the undifferentiated IP14D-1 and mESCs, nor were the expressions of Mvh and Stra8 between iEBs and EBs. IP14D-1 and iEBs had the potential to differentiate into iPGCs, which increased in number in the 7-day-old iEBs, and the expression of iPGC-differentiation associated Lin28 became lower in the older iEBs.
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November 2011

Identification of testosterone-/androgen receptor-regulated genes in mouse Sertoli cells.

Asian J Androl 2012 Mar 17;14(2):294-300. Epub 2011 Oct 17.

The Guangdong and Shenzhen Key Lab of Male Reproductive Medicine and Genetics, Sex Hormone Research Center, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China.

Androgen and androgen receptor (AR) play important roles in male spermatogenesis and fertility, yet detailed androgen/AR signals in Sertoli cells remain unclear. To identify AR target genes in Sertoli cells, we analyzed the gene expression profiles of testis between mice lacking AR in Sertoli cells (S-AR(-/y)) and their littermate wild-type (WT) mice. Digital gene expression analysis identified 2276 genes downregulated and 2865 genes upregulated in the S-AR(-/y) mice testis compared to WT ones. To further nail down the difference within Sertoli cells, we first constructed Sertoli cell line TM4 with stably transfected AR (named as TM4/AR) and found androgens failed to transactivate AR in Sertoli TM4 and TM4/AR cells. Interestingly, additional transient transfection of AR-cDNA resulted in significant androgen responsiveness with TM4/AR cells showing 10 times more androgen sensitivity than TM4 cells. In the condition where maximal androgen response was demonstrated, we then analyzed gene expression and found the expression levels of 2313 genes were changed more than twofold by transient transfection of AR-cDNA in the presence of testosterone. Among these genes, 603 androgen-/AR-regulated genes, including 164 upregulated and 439 downregulated, were found in both S-AR(-/y) mice testis and TM4/AR cells. Using informatics analysis, the gene ontology was applied to analyze these androgen-/AR-regulated genes to predict the potential roles of androgen/AR in the process of spermatogenesis. Together, using gene analysis in both S-AR(-/y) mice testis and TM4/AR cells may help us to better understand the androgen/AR signals in Sertoli cells and their influences in spermatogenesis.
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http://dx.doi.org/10.1038/aja.2011.94DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735086PMC
March 2012

[Abnormal expression and significance of MIR-184 in human renal carcinoma].

Beijing Da Xue Xue Bao Yi Xue Ban 2011 Aug;43(4):509-13

Department of Reproductive Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China.

Objective: To explore the role of microRNA-184(MIR-184) in the development of renal cell carcinoma(RCC).

Methods: The expressions of MIR-184 in 51 patients with RCC Investigated, normal adjacent tissues (ADTs) matched by fluorescence quantitative PCR technology (RT-qPCR) and the correlations analyzed between MIR-184 expression and the age, gender and clinical stage of RCC patients.

Results: The average expression of MIR-184 in RCC was -14.664 6 ± 5.362 4, while that in ADTs was -10.408 7 ± 3.482 7(P<0.01). Bounded with the MIR-184 expression in RCC, patients were divided into lower-expression group and higher-expression group. Meanwhile, the RCC patients were divided into three groups according to the age, gender and clinical stage of the patients. Chi-square statistical analysis showed that the expression level of MIR-184 was not significantly correlated with the patient's age, gender and clinical stage (respectively: P>0.03, P>0.99, P>0.03).

Conclusion: MIR-184 in RCC was significantly lower than that in ADTs, which may have potential significance in the occurrence and development of RCC.
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August 2011

[The progress of TMPRSS2-ETS gene fusions and their mechanism in prostate cancer].

Yi Chuan 2011 Feb;33(2):117-22

The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen 518036, China.

The gene fusions between transmembrane protease serine 2 (TMPRSS2) and E26 (ETS) transcription factors are present in over 50% of patients with prostate cancer. TMPRSS2-ERG is the most common gene fusion type. The ERG overexpression induced by TMPRSS2-ERG gene fusion contributes to the development of prostate cancer. Both androgen receptor binding and genotoxic stress induce chromosomal proximity and TMPRSS2-ETS gene fusions. TMPRSS2-ERG gene fusion functions as a biomarker for prostate cancer, which can be easily detected in urine. This review focuses on the characteristics, oncogenic and rearranged mechanism, and clinical application of TMPRSS2-ETS gene fusions.
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http://dx.doi.org/10.3724/sp.j.1005.2011.00117DOI Listing
February 2011

Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54.

Nat Genet 2010 Sep 22;42(9):759-63. Epub 2010 Aug 22.

Cancer Research Center, Xinxiang Medical University, Xinxiang, Henan, China.

We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.
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http://dx.doi.org/10.1038/ng.648DOI Listing
September 2010

[Y chromosome microdeletion and male infertility: past, present and future].

Authors:
Zhi-ming Cai

Zhonghua Nan Ke Xue 2010 May;16(5):387-94

Guangdong Key Laboratory of Male Reproductive Medicine and Genetics/Shenzhen PKU-HKUST Institute of Urology, Shenzhen PKU-HKUST Medical Center, Shenzhen Hospital of Peking University, Shenzhen, Guangdong 518036, China.

The spermatogenesis failure with a genetic defect is one of the major causes of male infertility. The Y chromosome is considered a lack of important functional genes. It was the discovery of the sex determining region Y that rekindled scientists'attention to the Y chromosome. The successful sequencing of the Y chromosome uncovered its actual structure and the molecular base of its microdeletion. Of the 220 Y chromosome genes (104 coding genes, 111 pseudogenes, and 5 other uncategorized genes), 16 coding genes have been found in the azoospermia factor region (AZF) and related with male fertility. To date, more than 12 Y chromosome microdeletions have been discovered in the AZF region. The amplicons regions in the Y chromosome are the genetic base of microdeletion occurrence. The Y chromosome microdeletions in the AZF region have been identified as a relatively common cause of male infertility and diagnosed by multiplex PCR in the clinical laboratory. Genomics has brought many revolutionized tools beneficial for better understanding the genetics of mal infertility and defining the role of the Y chromosome gene in spermatogenesis.
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May 2010

[Extracellular matrix regulates expressions of germ cell differentiation associated genes in mouse embryonic stem cells].

Zhonghua Nan Ke Xue 2009 Nov;15(11):967-73

Key Laboratory of Male Reproduction and Genetics of Guangdong Province, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, China.

Objective: Interactions of cells with the extracellular matrix (ECM) are essential for cell differentiation. The authors sought to determine the roles of different ECMs in the expressions of germ cell differentiation associated genes after mouse embryonic stem cells (mESCs) differentiated into embryoid bodies (EBs).

Methods: EBs derived from mESCs were maintained in suspension for 3 days and then cultured on the plates coated with various ECMs, including fibronectin (F), laminin (L), matrigel (M), collagen (C) and nonadhensive agarose (A), respectively, for 1, 2, 3 or 4 days, followed by evaluation of the expressions of the genes associated with germ cell differentiation by RT-PCR.

Results: The EBs of the F and L groups exhibited facilitated adherent differentiation. The expressions of the Blimp-1, Stella, Mvh and Stra8 genes were increased gradually in the F and L but not obviously in the M and C groups. The overall gene expressions were low in the A group, but high and then gradually decreased in the blank control group. Endogenous fibronectin, laminin and integrin beta1 were obviously expressed in the L and control groups.

Conclusion: Laminin /integrin beta1 signaling may play a role in regulating the differentiation of mESCs into primordial germ cells (PGCs). Exogenous laminin can facilitate the differentiation of mESC-derived EBs into PGCs by acting on the integrin beta1 subunit, while exogenous fibronectin may be involved in the regulation of the differentiation through other integrin subunit. Endogenous laminin and fibronectin secreted by EBs may also facilitate cell differentiation in the absence of exogenous ECMs.
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November 2009