Time filter

Source Type

Dong L.-H.,Institute of Basic Medicine | Wen J.-K.,Institute of Basic Medicine | Miao S.-B.,Institute of Basic Medicine | Jia Z.,Hebei Medical University | And 4 more authors.
Cell Research | Year: 2010

The increased proliferation and migration of vascular smooth muscle cells (VSMCs) are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown to induce apoptosis and growth inhibition in cancer cells through multiple pathways. However, the potential role of baicalin in regulation of VSMC proliferation and prevention of cardiovascular diseases remains unexplored. In this study, we show that pretreatment with baicalin has a dose-dependent inhibitory effect on PDGF-BB-stimulated VSMC proliferation, accompanied with the reduction of proliferating cell nuclear antigen (PCNA) expression. We also show that baicalin-induced growth inhibition is associated with a decrease in cyclin E-CDK2 activation and increase in p27 level in PDGF-stimulated VSMCs, which appears to be at least partly mediated by blockade of PDGF receptor Β (PDGFRΒ)-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. In addition, baicalin was also found to inhibit adhesion molecule expression and cell migration induced by PDGF-BB in VSMCs. Furthermore, using an animal carotid arterial balloon-injury model, we found that baicalin significantly inhibited neointimal hyperplasia. Taken together, our results reveal a novel function of baicalin in inducing growth arrest of PDGF-stimulated VSMCs and suppressing neointimal hyperplasia after balloon injury, and suggest that the underlying mechanism involves the inhibition of cyclin E-CDK2 activation and the increase in p27 accumulation via blockade of the PDGFRΒ-ERK1/2 signaling cascade. © 2010 IBCB, SIBS, CAS. All rights reserved.


Fang X.-M.,Institute of Basic Medicine | Liu B.,Institute of Basic Medicine | Liu Y.-B.,Hebei Medical University | Wang J.-J.,Institute of Basic Medicine | And 3 more authors.
Oncology Reports | Year: 2011

Acetylbritannilactone (ABL) is a new active compound isolated from Inula Britannica L, a traditional Chinese medicinal herb. It has been reported that ABL can inhibit the proliferation of vascular smooth muscle cells (VSMCs) and neointima formation after balloon injury in rats. ABL also shows chemopreventive properties by inducing cell apoptosis in breast and ovarian cancers, but the antitumor activity and the molecular targets of ABL in colon cancer cells have not been determined. In this study, we showed that ABL inhibits the growth in dose- and time-dependent manners by inducing cell cycle arrest in G0/G1 phase of HT-29 human colon cancer cells. This suppression was accompanied by a strong decrease of cyclin E and CDK4 protein levels, and an increase in p21 protein expression in HT-29 cells. We also show that ABL-induced growth inhibition is associated with the upregulation of KLF4 expression. The overexpression of KLF4 by infection with pAd-KLF4 resulted in growth inhibition, with decrease in the protein levels of cyclin E and CDK4, and increase in the expression of p21, similarly to the effects of ABL. Conversely, knockdown of KLF4 using a specific siRNA impaired the ABL-induced growth inhibition in HT-29 cells. These results suggest that KLF4 as an important cellular target of ABL mediates the growth inhibition of HT-29 cells induced by ABL via upregulation of p21 expression.


Mei Q.,Institute of Basic Medicine | Li X.,Institute of Basic Medicine | Guo M.,Institute of Basic Medicine | Fu X.,Institute of Basic Medicine | And 2 more authors.
Expert Review of Anticancer Therapy | Year: 2014

The dysregulation of cell signaling plays a pivotal role in tumorigenesis and progression. miRNAs have been linked to almost all known aspects of physiological and pathological processes. It is well known that the miRNA network is linked at several and unexpected levels with cancer-related signaling pathways. Our understanding of the roles and regulation of the miRNA network has been extended to include classical cell signaling, termed miRNA network complements cell signaling in cancer. As a transcription factor, tumor suppressor p53 plays a central role in tumor prevention. Recent studies have demonstrated that miRNAs may regulate the expression of the p53 pathway or be regulated by the p53 pathway. These findings added a new and challenging layer of complexity to the p53 pathway and prompted us to contemplate the use of the compensatory mechanisms in therapeutics against cancer. In this review, we have therefore summarized the p53 tumor suppressive pathway as a typical paradigm to elucidate the advances of the compensatory mechanisms. We then go on to critically discuss how the compensatory mechanisms can be used to enable better cancer diagnosis and prognosis and to serve as potential therapeutic targets. © Informa UK, Ltd.


Dai H.,Institute of Basic Medicine | Dai H.,Chinese PLA General Hospital | Wang Y.,Institute of Basic Medicine | Wang Y.,Chinese PLA General Hospital | And 3 more authors.
Journal of the National Cancer Institute | Year: 2016

The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy. © The Author 2016. Published by Oxford University Press.


PubMed | Chinese PLA General Hospital
Type: | Journal: Clinical cancer research : an official journal of the American Association for Cancer Research | Year: 2016

Relapsed or refractory Hodgkin lymphoma is a challenge for medical oncologists because of poor overall survival. We aimed to assess the feasibility, safety, and efficacy of CD30-targeting CAR T cells in patients with progressive relapsed or refractory Hodgkin lymphoma.Patients with relapsed or refractory Hodgkin lymphoma received a conditioning chemotherapy followed by the CART-30 cell infusion. The level of CAR transgenes in peripheral blood and biopsied tumor tissues was measured periodically according to an assigned protocol by quantitative PCR (qPCR).Eighteen patients were enrolled; most of whom had a heavy treatment history or multiple tumor lesions and received a mean of 1.56 10CART-30 cell therapy was safe, feasible, and efficient in relapsed or refractory lymphoma and guarantees a large-scale patient recruitment. Clin Cancer Res; 1-11. 2016 AACR.


Guo L.,Qinghai University | Li X.,Institute of Basic Medicine | Guo Z.,Qinghai University
Journal of Materials Science: Materials in Electronics | Year: 2015

Novel nonlinear optical chromophore with strong electron donor, diazo electron bridge and isolation groups on both sides were synthesized and characterized by mass spectrum and hydrogen nuclear magnetic resonance. Strong electron donor and diazo electron bridge improve the nonlinear optical activities of the chromophore, large and reactive isolated groups improve the chromophore’s solubility and reduced the interaction among the chromophores. Second order nonlinear optical polymers with different chromophore loading densities were prepared and showed us the smallest glass transition temperature change. Large second order nonlinear optical coefficients were also gotten by second harmonic generation method 15.3, 27.2 and 33.4 pm/V for chromophore loading density at 10, 22.5 and 27.5 wt% respectively. © 2015, Springer Science+Business Media New York.


Canbin O.,Chinese Academy of Agricultural Sciences | Li X.,Institute of Basic Medicine | Cao A.,Chinese Academy of Agricultural Sciences
Materials Letters | Year: 2016

Functional molecules with D-π-A structure were introduced to a new application direction of seed sterilization. According to the specific requirement of seed sterilization, two carboxyl groups were introduced to D-π-A molecules both in donor group and acceptor group. Such a modification improved the solubility of D-π-A molecule and the adhesion between D-π-A molecule and the surface of seed. Else, the functional D-π-A molecule prepared in this manuscript also showed us low delocalized energy and poor intermolecular interaction. The d33 value of chromophore a-COOH was also measured. Due to the poor donor and solubility in polycarbonate, the largest d33 value was just 16.2 pm/V. © 2016 Elsevier B.V.


Zhou J.,Chinese Academy of Sciences | Li X.,Institute of Basic Medicine | Wang M.,Chinese Academy of Sciences
Materials Letters | Year: 2016

Organic nonlinear optical chromophores with different number of N atoms were prepared and characterized. Their nonlinear optical character was studied both by theoretical calculation and second harmonic generation experiment. Chromophore ZJ1 showed us the largest d33 value of 87.5 pm/V. More importantly, the photochemistry stability of the chromophores was also studied in details. Chromophores with N atoms in the conjugated system showed us better photochemistry stability than the traditional chromophores. © 2016 Elsevier B.V.


Canbin O.,Chinese Academy of Agricultural Sciences | Li X.,Institute of Basic Medicine | Cao A.,Chinese Academy of Agricultural Sciences
Materials Letters | Year: 2015

In order to explore the application of organic D-π-A molecules in bio-imaging, novel D-π-A molecule (chromophore OY) with multi-hydroxyl groups was designed and synthesized. Compared to the traditional D-π-A molecule, chromophore OY showed us great improvement in water solubility. The solubility of chromophore OY in water could reach 200 ppm. Else, the thermal stability of chromophore OY was also studied. Due to the presence of multi-hydroxyl groups, the thermal stability of chromophore OY was not very good. The initial decomposition temperature was just above 100°C, which was attributed to the dehydration of the hydroxyl groups. Though the SHG effect is not very high, it is large enough for the detection of SHG signal in water solution (0.2-0.3 pm/V). © 2015 Elsevier B.V. All rights reserved.


PubMed | Institute of Basic Medicine
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

10676 Background: Aberrant ER activity is linked to genesis and malignant progression of breast cancer through direct target gene activation or repression. A complex network of coregulatory proteins is largely believed to determine the transcriptional activity of ER. LRP16 was identified previously to be an estrogen (E2) responsive gene, but its function involving in conferring estrogen signalling pathway is not clear.Endogenous LRP16 expression in MCF-7 cells was stably suppressed by retrovirus-mediated small interference RNA (siRNA). The effects of LRP16 expression on E2-stimulated growth and invasive ability of MCF-7 cells were determined in vitro and in vivo assays. The effects of LRP16 expression on ER transactivation were determined by luciferase assays. The interaction of LRP16 and ER was examined by GST pull-down and coimmunopricipitation (CoIP) assays. Northern blot and Western blot were used to detect the mRNA and protein levels of ER target genes in LRP16-inhibited MCF-7 cells. The LRP16 expression levels in primary breast cancer were detected by Northern blot.Fristly, LRP16 expression was characterized to be dependent on estrogen activities. Then, LRP16 was identified to be an estrogen-independent ER cofactor in ER-positive breast cancer cells and demonstrate that LRP16 is an essential coactivator to ER-mediated transactivation in an estrogen-dependent manner. Suppression of LRP16 expression in ER-positive breast cancer cells specifically inhibits the transcription of ER upregulated genes, results in the increase of E-cadherin expression through ER mediation. In vitro and in vivo data demonstrate that suppression of LRP16 inhibits the ability of estrogen-stimulated proliferation and invasiveness of ER-positive breast cancer cells. The pathological and clinical characteristics of human breast cancer includining ER/PR-positiveness, tumor diameter and the involvement of axillary lymphoid nodes were tightly linked with the LRP16 gene expression level.These results establish a mechanistic link between estrogen receptor status, its coactivator LRP16, and progression of ER-positive breast cancers, and may provide a novel antiestrogenic target for the therapy of ER positive breast cancer. No significant financial relationships to disclose.

Loading Institute of Basic Medicine collaborators
Loading Institute of Basic Medicine collaborators