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Dive into the research topics where Xiao Yan Zhong is active.

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Featured researches published by Xiao Yan Zhong.


Prenatal Diagnosis | 2000

Fetal DNA in maternal plasma is elevated in pregnancies with aneuploid fetuses

Xiao Yan Zhong; Martin R. Bürk; Carolyn Troeger; Laird R. Jackson; Wolfgang Holzgreve; Sinuhe Hahn

Current non‐invasive screening methods for the prenatal diagnosis of fetal aneuploidies are hampered by low sensitivities and high false positive rates. Attempts to redress this situation include the enrichment of fetal cells from maternal blood, or the use of fetal DNA in the plasma of pregnant women. By the use of real‐time quantitative polymerase chain reaction (PCR) it has recently been shown that circulatory male fetal DNA in maternal plasma is elevated in pregnancies with trisomy 21 fetuses. In this independent study we confirm and extend upon these results by showing that the levels of fetal DNA are also elevated in pregnancies with other chromosomal aneuploidies (mean=185.8 genome equivalents/ml; range=62.2–471.7) when compared to pregnancies with normal male fetuses (mean=81.9 genome equivalents/ml; range=28.8–328.9), p=0.005. This elevation was greatest for fetuses with trisomy 21, whereas it was not significant for fetuses with trisomy 18, p=0.356. These data suggest that a quantitative analysis of such fetal DNA levels may serve as an additional marker for certain fetal chromosomal abnormalities, in particular for trisomy 21. Copyright


Hypertension in Pregnancy | 2002

THE LEVELS OF CIRCULATORY FETAL DNA IN MATERNAL PLASMA ARE ELEVATED PRIOR TO THE ONSET OF PREECLAMPSIA

Xiao Yan Zhong; Wolfgang Holzgreve; Sinuhe Hahn

Objective: Elevations in cell free fetal DNA has previously been determined in pregnancies affected by preeclampsia. A recent report has indicated that cell free fetal DNA concentrations are elevated early in pregnancy before disease onset. As we have recently performed a prospective study to examine fetal cell traffic in pregnancies at risk for developing preeclampsia, we now quantify cell free fetal DNA concentrations in these samples. Methods: Blood samples were collected in the second trimester of pregnancy from pregnancies at risk for preeclampsia. Cell free fetal DNA amounts were quantified by real-time PCR. These results were then correlated with subsequent pregnancy outcome. Results: Free fetal DNA levels were significantly higher (median of 422.9 vs. 128.5 copies/mL maternal plasma; p=0.005) in plasma samples from women who developed preeclampsia (n=10) when compared to those who had unremarkable pregnancies (n=40). Conclusions: Our data independently confirm the finding that maternal plasma cell free fetal DNA levels are elevated early in pregnancies, which later develop preeclampsia.


British Journal of Obstetrics and Gynaecology | 2000

Detection of fetal Rhesus D and sex using fetal DNA from maternal plasma by multiplex polymerase chain reaction

Xiao Yan Zhong; Wolfgang Holzgreve; Sinuhe Hahn

Objective To test the sensitivity, specificity and reproducibility using fetal DNA obtained from plasma of pregnant women by polymerase chain reaction for the simultaneous detection of both fetal sex and Rhesus D genotype.


Molecular Cancer | 2009

Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors

Corina Kohler; Ramin Radpour; Zeinab Barekati; Reza Asadollahi; Johannes Bitzer; Edward Wight; Nicole Bürki; Claude Diesch; Wolfgang Holzgreve; Xiao Yan Zhong

BackgroundWith the aim to simplify cancer management, cancer research lately dedicated itself more and more to discover and develop non-invasive biomarkers. In this connection, circulating cell-free DNA (ccf DNA) seems to be a promising candidate. Altered levels of ccf nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) have been found in several cancer types and might have a diagnostic value.MethodsUsing multiplex real-time PCR we investigated the levels of ccf nDNA and mtDNA in plasma samples from patients with malignant and benign breast tumors, and from healthy controls. To evaluate the applicability of plasma ccf nDNA and mtDNA as a biomarker for distinguishing between the three study-groups we performed ROC (Receiver Operating Characteristic) curve analysis. We also compared the levels of both species in the cancer group with clinicopathological parameters.ResultsWhile the levels of ccf nDNA in the cancer group were significantly higher in comparison with the benign tumor group (P < 0.001) and the healthy control group (P < 0.001), the level of ccf mtDNA was found to be significantly lower in the two tumor-groups (benign: P < 0.001; malignant: P = 0.022). The level of ccf nDNA was also associated with tumor-size (<2 cm vs. >2 cm<5 cm; 2250 vs. 6658; Mann-Whitney-U-Test: P = 0.034). Using ROC curve analysis, we were able to distinguish between the breast cancer cases and the healthy controls using ccf nDNA as marker (cut-off: 1866 GE/ml; sensitivity: 81%; specificity: 69%; P < 0.001) and between the tumor group and the healthy controls using ccf mtDNA as marker (cut-off: 463282 GE/ml; sensitivity: 53%; specificity: 87%; P < 0.001).ConclusionOur data suggests that nuclear and mitochondrial ccf DNA have potential as biomarkers in breast tumor management. However, ccf nDNA shows greater promise regarding sensitivity and specificity.


Prenatal Diagnosis | 2008

Digital PCR: a powerful new tool for noninvasive prenatal diagnosis?

Bernhard G. Zimmermann; Simon Grill; Wolfgang Holzgreve; Xiao Yan Zhong; Laird G. Jackson; Sinuhe Hahn

Recent reports have indicated that digital PCR may be useful for the noninvasive detection of fetal aneuploidies by the analysis of cell‐free DNA and RNA in maternal plasma or serum. In this review we provide an insight into the underlying technology and its previous application in the determination of the allelic frequencies of oncogenic alterations in cancer specimens. We also provide an indication of how this new technology may prove useful for the detection of fetal aneuploidies and single gene Mendelian disorders. Copyright


PLOS ONE | 2011

Hypermethylation of Tumor Suppressor Genes Involved in Critical Regulatory Pathways for Developing a Blood-Based Test in Breast Cancer

Ramin Radpour; Zeinab Barekati; Corina Kohler; Qing Lv; Nicole Bürki; Claude Diesch; Johannes Bitzer; Hong Zheng; Seraina Schmid; Xiao Yan Zhong

Background Aberrant DNA methylation patterns might be used as a biomarker for diagnosis and management of cancer patients. Methods and Findings To achieve a gene panel for developing a breast cancer blood-based test we quantitatively assessed the DNA methylation proportion of 248 CpG sites per sample (total of 31,248 sites in all analyzed samples) on 10 candidate genes (APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P16, P21 and TIMP3). The number of 126 samples consisting of two different cohorts was used (first cohort: plasma samples from breast cancer patients and normal controls; second cohort: triple matched samples including cancerous tissue, matched normal tissue and serum samples). In the first cohort, circulating cell free methylated DNA of the 8 tumor suppressor genes (TSGs) was significantly higher in patients with breast cancer compared to normal controls (P<0.01). In the second cohort containing triple matched samples, seven genes showed concordant hypermethylated profile in tumor tissue and serum samples compared to normal tissue (P<0.05). Using eight genes as a panel to develop a blood-based test for breast cancer, a sensitivity and specificity of more than 90% could be achieved in distinguishing between tumor and normal samples. Conclusions Our study suggests that the selected TSG panel combined with the high-throughput technology might be a useful tool to develop epigenetic based predictive and prognostic biomarker for breast cancer relying on pathologic methylation changes in tumor tissue, as well as in circulation.


Prenatal Diagnosis | 2000

High levels of fetal erythroblasts and fetal extracellular DNA in the peripheral blood of a pregnant woman with idiopathic polyhydramnios: case report

Xiao Yan Zhong; Wolfgang Holzgreve; Jin Chun Li; Kilic Aydinli; Sinuhe Hahn

Abnormal amniotic fluid volume can be associated with increased maternal risk as well as perinatal morbidity and mortality. Polyhydramnios is often indicative of fetal, placental or maternal problems. In a large proportion of patients the aetiology of the disorder is unclear. Here we report on a case in which numerous fetal erythroblasts and large quantities of extracellular fetal DNA were found in the peripheral blood of a pregnant woman with idiopathic polyhydramnios bearing a male fetus. Following enrichment of erythroblasts by magnetic separation (MACS) and anti‐CD71 antibodies, approximately 45‐fold more erythroblasts were determined per ml peripheral maternal blood than in matched controls (231 versus 5). Single cell multiplex polymerase chain reaction (PCR) of individually micromanipulated erythroblasts showed that approximately 122 of these were of fetal origin. The concentration of extracellular fetal circulatory DNA in maternal plasma was determined by real‐time quantitative PCR and shown to be almost double that of the control group (749.2 versus 404 fetal genome equivalents per ml maternal plasma). It can be speculated that the increased intrauterine pressure in polyhydramnios leads to an enhanced influx of fetal cells and free extracellular fetal DNA into the maternal circulation. This hypothesis will have to be tested with further cases. Copyright


Obstetrics & Gynecology | 2000

Fluctuation of maternal and fetal free extracellular circulatory DNA in maternal plasma.

Xiao Yan Zhong; Martin R. Bürk; Carolyn Troeger; Anjeung Kang; Wolfgang Holzgreve; Sinuhe Hahn

Objective To examine whether concentrations of free extra-cellular fetal circulatory DNA in maternal plasma are stable or fluctuate. Methods Consecutive blood samples were drawn from 13 healthy nonpregnant volunteers and from 16 healthy pregnant women over 3 days. DNA was isolated from the plasma fraction and quantified by real-time polymerase chain reaction (PCR). Results In nonpregnant controls the total amount of cell free DNA fluctuated by an average of 13.5-fold. In samples obtained from pregnant women the amount of maternal cell free DNA varied by an average of 21.5-fold. Because ten of those women were pregnant with male fetuses, the concentration of free fetal DNA in these cases was determined by a real-time PCR assay for the Y chromosome. The mean variation in free fetal DNA levels in male fetuses was 2.2-fold. Conclusion The degree of variation in free fetal DNA concentrations observed in this study was similar to published values, so these results imply that care should be exercised when considering quantitation of this fetal material for potential diagnostic or screening purposes.


Cellular and Molecular Life Sciences | 2000

Current applications of single-cell PCR

Sinuhe Hahn; Xiao Yan Zhong; Carolyn Troeger; R. Burgemeister; K. Gloning; Wolfgang Holzgreve

Abstract. The advent of the polymerase chain reaction (PCR) has revolutionised the way in which molecular biologists view their task at hand, for it is now possible to amplify and examine minute quantities of rare genetic material: the limit of this exploration being the single cell. It is especially in the field of prenatal diagnostics that this ability has been readily seized upon, as it has opened up the prospect of preimplantation genetic analysis and the use of fetal cells enriched from the blood of pregnant women for the assessment of single-gene Mendelian disorders. However, apart from diagnostic applications, single-cell PCR has proven to be of enormous use to basic scientists, addressing diverse immunological, neurological and developmental questions, where both the genome but also messenger RNA expression patterns were examined. Furthermore, recent advances, such as optimised whole genome amplification (WGA) procedures, single-cell complementary DNA arrays and perhaps even single-cell comparative genomic hybridisation will ensure that the genetic analysis of single cells will become common practice, thereby opening up new possibilities for diagnosis and research.


Annals of the New York Academy of Sciences | 2006

CIRCULATORY FETAL AND MATERNAL DNA IN PREGNANCIES AT RISK AND THOSE AFFECTED BY PREECLAMPSIA

Xiao Yan Zhong; Wolfgang Holzgreve; Sinuhe Hahn

Abstract: Elevations in fetal cell traffic as well as increased release of cell‐free fetal DNA into the maternal periphery have previously been shown to occur in pregnancies affected by preeclampsia. Our own investigations have shown that manifestation of preeclampsia is associated with an increased accumulation of circulatory fetal DNA as well as cell‐free maternal DNA in maternal plasma. We further established that the increments in these two molecular genetic analytes corresponded to the severity of the disease and to each other. This latter phenomenon was evident in preeclamptic pregnancies, but not in normal ones. As we had recently performed a prospective study to investigate fetal cell traffic prior to onset of preeclamptic symptoms, we examined the levels of cell‐free fetal and maternal DNA in these samples. This analysis indicated that circulatory fetal DNA concentrations were significantly elevated prior to onset of the disease symptoms. No similar feature was observed for cell‐free maternal DNA levels.

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