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Ying Peng

Publications and source records attributed to Ying Peng.

66 records · Page 4Linked to original sources

Tyrosine kinase inhibitor STI-571/Gleevec down-regulates the beta-catenin signaling activity.

Beta-Catenin is a critical transducer of the Wnt signal pathway and plays an important role in many developmental and cellular processes. Deregulation of beta-catenin signaling has been observed in a broad range of human tumors. In this report, we investigated whether tyrosine kinase inhibitor STI-571 could inhibit the beta-catenin signaling activity and hence suppress cell proliferation. Our results demonstrated that STI-571 effectively inhibited the constitutive activity of beta-catenin signaling in human colon cancer cells as well as the Wnt1-induced activation of beta-catenin signaling in HOS, HTB-94, and HEK 293 cells. Furthermore, STI-571 was shown to effectively suppress the proliferation of human colon cancer cells. Finally, we demonstrated that the Wnt1-mediated activation of a GAL4-beta-catenin heterologous transcription system was effectively inhibited by STI-571. Thus, our findings suggest that tyrosine phosphorylation may play an important role in regulating beta-catenin signaling activity, and inhibition of this signaling pathway by STI-571 may be further explored as an important target for alternative/adjuvant treatments for a broader range of human cancer.

Adenoviridae↗

Spasmodic dysphonia in a patient with the A to G transition at nucleotide 8344 in mitochondrial DNA.

Dystonia has been described in various diseases affecting mitochondrial function but spasmodic dysphonia, a form of focal dystonia, has not. We present a patient with action myoclonus affecting the hands and arms who carried the most common mutation in mitochondrial DNA causing the myoclonic epilepsy and ragged red fibers (MERRF) syndrome (the A-->G substitution at nucleotide 8344 in the tRNA(Lys) gene). This patient also had spasmodic dysphonia that was responsive to treatment with intralaryngeal botulinum toxin.

DNA, Mitochondrial↗

A limited sampling method for the estimation of serum calcitriol area under the curve in cancer patients.

Pharmacokinetic (PK) data from 34 cancer patients receiving 2 to 10 micrograms of calcitriol subcutaneously (s.c.) were used to develop a limited sampling method for predicting serum calcitriol area under curve (AUC) based on three samples instead of the full complement of 12 to 16 samples. Serum calcitriol levels were measured by 1, 25-dihydroxyvitamin D3-[I125] radioimmunoassay. Individual patient-corrected serum calcitriol AUC0-12 h was calculated by the trapezoidal rule after subtracting the pretreatment serum calcitriol level. PK data were split into "training" and "evaluation" sets based on calcitriol dose and chronological order of enrollment. Linear regression models of log-corrected AUC0-12 h versus individual log calcitriol serum levels in the hour 1, 2, 3, 4, 6, and 8 samples were established using the training data set of 17 patients. The fit was tested on the evaluation data set of 17 patients using mean squared error (MSE) as the fit criterion. The best single time point predictor of log AUC0-12 h was the log serum (calcitriol) at hour 6 (MSE = 0.0061). The best prediction of log AUC0-12 h using two time points was found to involve hour 6 and hour 2 (MSE = 0.0018). The prediction equation for the latter model was as follows: Log AUC = 1.125 + 0.3756.log (calcitriol) at hour 2 + 0.5859.log (calcitriol) at hour 6. This limited sampling method was further evaluated in 83 cancer patients treated with 4 to 38 micrograms of oral (p.o.) calcitriol; observed and predicted calcitriol AUC0-12 h were highly correlated (r > or = 0.90, p = 0.0001). These results show that serum calcitriol AUC0-12 h after s.c. and p.o. calcitriol administration is accurately estimated using pretreatment and 2- and 6-hour blood samples.

Area Under Curve↗

Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs).

BACKGROUND: Bone morphogenic proteins (BMPs) are known to promote osteogenesis, and clinical trials are currently underway to evaluate the ability of certain BMPs to promote fracture-healing and spinal fusion. The optimal BMPs to be used in different clinical applications have not been elucidated, and a comprehensive evaluation of the relative osteogenic activity of different BMPs is lacking. METHODS: To identify the BMPs that may possess the most osteoinductive activity, we analyzed the osteogenic activity of BMPs in mesenchymal progenitor and osteoblastic cells. Recombinant adenoviruses expressing fourteen human BMPs (BMP-2 to BMP-15) were constructed to infect pluripotent mesenchymal progenitor C3H10T1/2 cells, preosteoblastic C2C12 cells, and osteoblastic TE-85 cells. Osteogenic activity was determined by measuring the induction of alkaline phosphatase, osteocalcin, and matrix mineralization upon BMP stimulation. RESULTS: BMP-2, 6, and 9 significantly induced alkaline phosphatase activity in pluripotential C3H10T1/2 cells, while BMP-2, 4, 6, 7, and 9 significantly induced alkaline phosphatase activity in preosteoblastic C2C12 cells. In TE-85 osteoblastic cells, most BMPs (except BMP-3 and 12) were able to induce alkaline phosphatase activity. The results of alkaline phosphatase histochemical staining assays were consistent with those of alkaline phosphatase colorimetric assays. Furthermore, BMP-2, 6, and 9 (as well as BMP-4 and, to a lesser extent, BMP-7) significantly induced osteocalcin expression in C3H10T1/2 cells. In C2C12 cells, osteocalcin expression was strongly induced by BMP-2, 4, 6, 7, and 9. Mineralized nodules were readily detected in C3H10T1/2 cells infected with BMP-2, 6, and 9 (and, to a lesser extent, those infected with BMP-4 and 7). CONCLUSIONS: A comprehensive analysis of the osteogenic activity of fourteen types of BMPs in osteoblastic progenitor cells was conducted. Our results suggest an osteogenic hierarchical model in which BMP-2, 6, and 9 may play an important role in inducing osteoblast differentiation of mesenchymal stem cells. In contrast, most BMPs are able to stimulate osteogenesis in mature osteoblasts.

Adenoviridae↗

Circadian rhythms in Drosophila.

We discuss some historical features of the circadian in Drosophila melanogaster. We then describe some recent progress from our laboratory in three different areas. First, we discuss the regulation of circadian gene expression as assayed with microarrays. Results are discussed that verify and extend published data, both with respect to the previously identified cycling mRNAs as well as some clustering within the genome of some of the genes that give rise to these circadian transcripts. Also discussed are experiments that attempt to identify transcripts that are enriched in lateral neurons, the key circadian pacemaker cells in the Drosophila brain. Second, the issue of damping within the brain is addressed, by assaying molecular oscillations after many days in constant darkness. Third, the identification of a new circadian mutant is described, which is a fully recessive allele of the gene Clock. The previous allele in flies, as well as the single mutant allele in mice, is a dominant allele. This limits the conclusions that can be drawn from the genetic and molecular analyses in these mutant strains. Results with the new recessive allele not only support the notion that Clock is an important clock gene but also indicate that it contributes more to the amplitude of the rhythm rather than the period.

Animals↗

Induction of apoptosis and inhibition of cell growth by developmental regulator hTBX5.

T box (Tbx) genes are a large family of transcription regulators that play critical roles in invertebrate and vertebrate development. Mutations in Tbx5 gene have been found to cause Holt-Oram syndrome (HOS) in humans. Partial dysfunction of TBX5 in mouse also causes HOS phenotype. Little is known about its molecular and cellular mechanism. Here, we report that ectopic expression of TBX5 inhibited colony formation, induced apoptosis, and decreased the growth rate of cells. The two point mutations in T domain and a truncated mutation in C-terminal found in human HOS patients produced TBX5 mutant proteins with a significantly reduction of colony suppression activity. Deletion of the DNA-binding domain, however, nearly completely abrogated its ability to suppress colony formation. These results reveal TBX5 as a new regulator of apoptosis and cell growth, suggesting a possible mechanism for Holt-Oram syndrome, and a potential reagent for controlling tumor growth.

Animals↗

Retina dorsal/ventral patterning by Xenopus TBX3.

Although it is well known that patterning in the retina of vertebrates is essential for retina formation and for the retinotopic projection of axons in the embryo, knowledge of molecular and cellular mechanisms of retina patterning is limited. We have previously identified the Xenopus Tbx3 gene (XTbx3) which is expressed in the dorsal retina but not in the ventral retina in Xenopus embryos [H. Li, C. Tierney, L. Wen, J. Y. Wu, and Y. Rao (1997) Development 124, 603-615; M.-L. He, L. Wen, C. E. Campbell, J. Y. Wu, and Y. Rao (1999) Proc. Natl. Acad. Sci. USA 96, 10212-10217]. Dosage-sensitive phenotypes in humans suggest that the manipulation of the amount and location of its products could be informative for understanding its normal function. Here we report that ectopic expression of Tbx3 by mRNA injection suppressed formation of the ventral retina. Furthermore, Tbx3 injection led to inhibition of molecular markers for the ventral retina including Pax-2 and netrin, indicating that Tbx3 plays an important role in retina dorsal/ventral patterning in vertebrates by inhibition of gene expression for ventral retina specification.

Animals↗

Whole CagA gene amplification of Helicobacter pylori and its fingerprinting by restriction fragment length polymorphism.

To set up a method of amplification for the whole CagA gene of Helicobacter pylori and its fingerprinting by restriction fragment length polymorphism (RFLP), nested PCR was employed in combination with TD-PCR to amplify the gene and EcoRI and Hind III were used to generate the RFLP fingerprinting. Target DNA fragments from 13 of 20 samples were successfully amplified and the relevant RFLP fingerprintings were obtained. It is concluded that the method can be used to amplify the whole CagA gene and CagA gene has apparent diversity of RFLP profile.

Antigens, Bacterial↗

Hypertensive epidemiology in Heilongjiang Province in China.

OBJECTIVE: To assess the epidemiology features of hypertension in Heilongjiang Province, China. METHODS: From 1959 to 1999, 289,157 people in total, ages > or = 15-year old (male 154,091, female 135,066) were investigated four times by a stratified chunk method in rural and urban areas in Heilongjiang Province. After a staff training program, this survey on blood pressure and risk factors was carried out under a worldwide uniform protocol with standardized method and interrelated quality control regulation. Among these samples, 1615 people (male 824, female 791) received blood-lipid analysis. RESULTS: The hypertensive incidence of Heilongjiang was much higher than the average level in China (P < 0.01) and it has gotten higher from 1959 to 1999, especially in the last ten years. It increased more in males than in females (P < 0.01). It was also higher with age. The mean age of hypertensive onset became ten years younger recently. It is different in different areas and professions. Age, BMI (body mass index), drinking alcohol, gender, history of maternal hypertension, high salt diet and professional status were the main risk factors for hypertension in Heilongjiang Province in China. CONCLUSION: The prophylaxis and treatment of hypertension should be enhanced in this area.

Adolescent↗

[REP-PCR analysis of Helicobacter pylori clinical strains].

Helicobacter pylori strains isolated from 20 gastritis patients and 20 peptic ulcer patients was genotyped by REP-PCR and was clustered with SAS software. These strains are divided into two categories according to their genotype. But the rate of the two sources of strain in the two categories shows no apparent difference(P approximately 0.1), indicating that there is no significant close relationship between the genotype and the pathogenicity.

English Abstract↗