1.Prediction of the microRNAs related to cardiovascular diseases by bioinformatics
Fan ZHANG ; Ming LU ; Qipeng ZHANG ; Fuchun ZHANG ; Wei GAO ; Qinghua CUI
Journal of Peking University(Health Sciences) 2004;0(01):-
Objective:To predict the microRNAs(miRNAs) related to cardiovascular diseases.Methods: Bioinformatics was used to find all cardiovascular disease related and cardiovascular function related protein-coding genes,and miRNAs were identified that localized the same transcription units as the above genes.Then other cardiovascular disease related miRNAs were identified by an miRNAs set and family analysis and Gene Ontology(GO).Results: Twenty potential cardiovascular disease related miRNAs were predicted from 626 cardiovascular disease related miRNAs,five of which had been confirmed by experiments.Conclusion: This study is of great help for the diagnosis and research of cardiovascular diseases,but the final conclusions need to be confirmed by experiments.
2.Tumor shrinkage by cyclopamine tartrate through inhibiting hedgehog signaling.
Qipeng FAN ; Dongsheng GU ; Miao HE ; Hailan LIU ; Tao SHENG ; Guorui XIE ; Ching-Xin LI ; Xiaoli ZHANG ; Brandon WAINWRIGHT ; Arash GARROSSIAN ; Massoud GARROSSIAN ; Dale GARDNER ; Jingwu XIE
Chinese Journal of Cancer 2011;30(7):472-481
The link of hedgehog (Hh) signaling activation to human cancer and synthesis of a variety of Hh signaling inhibitors raise great expectation that inhibiting Hh signaling may be effective in human cancer treatment. Cyclopamine (Cyc), an alkaloid from the Veratrum plant, is a specific natural product inhibitor of the Hh pathway that acts by targeting smoothened (SMO) protein. However, its poor solubility, acid sensitivity, and weak potency relative to other Hh antagonists prevent the clinical development of Cyc as a therapeutic agent. Here, we report properties of cyclopamine tartrate salt (CycT) and its activities in Hh signaling-mediated cancer in vitro and in vivo. Unlike Cyc, CycT is water soluble (5-10 mg/mL). The median lethal dose (LD50) of CycT was 62.5 mg/kg body weight compared to 43.5 mg/kg for Cyc, and the plasma half-life (T1/2) of CycT was not significantly different from that of Cyc. We showed that CycT had a higher inhibitory activity for Hh signaling-dependent motor neuron differentiation than did Cyc (IC50 = 50 nmol/L for CycT vs. 300 nmol/L for Cyc). We also tested the antitumor effectiveness of these Hh inhibitors using two mouse models of basal cell carcinomas (K14cre:Ptch1(neo/neo) and K14cre:SmoM2(YFP)). After topical application of CycT or Cyc daily for 21 days, we found that all CycT-treated mice had tumor shrinkage and decreased expression of Hh target genes. Taken together, we found that CycT is an effective inhibitor of Hh signaling-mediated carcinogenesis.
Animals
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Carcinoma, Basal Cell
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pathology
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Cell Differentiation
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drug effects
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Embryonic Stem Cells
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cytology
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Hedgehog Proteins
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antagonists & inhibitors
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metabolism
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Mice
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Motor Neurons
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cytology
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Plants, Medicinal
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chemistry
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Receptors, G-Protein-Coupled
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antagonists & inhibitors
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metabolism
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Signal Transduction
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drug effects
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Skin Neoplasms
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pathology
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Smoothened Receptor
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Solubility
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Tartrates
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blood
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pharmacology
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Tumor Burden
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drug effects
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Veratrum
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chemistry
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Veratrum Alkaloids
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blood
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isolation & purification
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pharmacology