Dimerization of urinary β-core/hCFβcf: a cause of poor β-core assay performance in Down syndrome screening studies

Iles, Ray K.; Butler, Stephen A.; Jacoby, Eli S.

doi:10.1002/(sici)1097-0223(199908)19:8<790::aid-pd627>3.0.co;2-z

Cited by 4 publications

(1 citation statement)

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“…However, not only did hCGβcf levels need to be corrected for gestational age, but adjustment had to be made for the dilutional effects of water intake and urination [ 15 ]. This meant that simple quantitated levels of hCGβcf per unit volume were so variable that performance as a single screening marker was not substantially greater, in terms of discriminatory power, than existing serum based analysis [ 16 - 18 ].…”

Section: Introductionmentioning

confidence: 99%

Direct and rapid mass spectral fingerprinting of maternal urine for the detection of Down syndrome pregnancy

et al. 2015

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BackgroundThe established methods of antenatal screening for Down syndrome are based on immunoassay for a panel of maternal serum biomarkers together with ultrasound measures. Recently, genetic analysis of maternal plasma cell free (cf) DNA has begun to be used but has a number of limitations including excessive turn-around time and cost. We aimed to develop an alternative method based on urinalysis that is simple, affordable and accurate.Method101 maternal urine samples sampled at 12–17 weeks gestation were taken from an archival collection of 2567 spot urines collected from women attending a prenatal screening clinic. 18 pregnancies in this set subsequently proved to be Down pregnancies. Samples were either neat urine or diluted between 10 to 1000 fold in dH2O and subjected to matrix assisted laser desorption ionization (MALDI), time of flight (ToF) mass spectrometry (MS). Data profiles were examined in the region 6,000 to 14,000 m/z. Spectral data was normalised and quantitative characteristics of the profile were compared between Down and controls.ResultsIn Down cases there were additional spectral profile peaks at 11,000-12,000 m/z and a corresponding reduction in intensity at 6,000-8,000 m/z. The ratio of the normalised values at these two ranges completely separated the 8 Down syndrome from the 39 controls at 12–14 weeks. Discrimination was poorer at 15–17 weeks where 3 of the 10 Down syndrome cases had values within the normal range.ConclusionsDirect MALDI ToF mass spectral profiling of maternal urinary has the potential for an affordable, simple, accurate and rapid alternative to current Down syndrome screening protocols.

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Section: Introductionmentioning

confidence: 99%

Direct and rapid mass spectral fingerprinting of maternal urine for the detection of Down syndrome pregnancy

et al. 2015

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Role of Glycoprotein Hormones in Endometrial Cancer

Bax

Davies²,

Chatzaki

et al. 2003

Cell and Molecular Biology of Endometrial Carcinoma

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et al. 2000

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Ectopic production of free beta human chorionic gonadotrophin (hCGβ) by bladder carcinoma is well described and occurs in approximately 35% of cases. hCGβ secreting tumours are more aggressive, radioresistant and have a greater propensity to metastasize. We proposed that the ectopic production of hCGβ was contributing in an autocrine fashion to the radioresistance and metastatic potential of such secreting tumours. Though we demonstrated that the addition of hCGβ to the culture media of bladder, cervical and endometrial carcinoma cell lines brought about an increase in cell populations this was not accompanied by a significant increase in the rate of replication. Since a cell population size is a balance of mitosis and mortality, we proposed that hCGβ was inhibiting apoptosis. Here we have demonstrated that following incubation with recombinant hCGβ, bladder carcinoma cells refrain from undergoing apoptosis. Quantitation of apoptotic bodies was carried out by immunoassay and corrected to cell number as determined by MTT assay. In each cell line, addition of hCGβ reduced the number of apoptotic bodies dose-dependently, indicating a diminished apoptotic rate. Furthermore, TGFβ1-induced apoptosis could be dose-dependently inhibited by co-incubation with hCGβ. We propose, therefore, that such a decline in apoptosis may account for the cell population increase previously reported. It may also explain the radioresistance and aggressive nature of hCGβ-secreting tumours and the poor prognosis associated therein. © 2000 Cancer Research Campaign

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Dimerization of urinary β-core/hCFβcf: a cause of poor β-core assay performance in Down syndrome screening studies

Cited by 4 publications

References 17 publications

Direct and rapid mass spectral fingerprinting of maternal urine for the detection of Down syndrome pregnancy

Direct and rapid mass spectral fingerprinting of maternal urine for the detection of Down syndrome pregnancy

Role of Glycoprotein Hormones in Endometrial Cancer

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