We investigated the expression and clinical significance of leptin receptor (OBR), p-STAT3 and p-AKT in patients with diffuse large B-cell lymphoma (DLBCL) by immunohistochemical analysis. Immunohistochemistry revealed high expression of OBR, p-STAT3 and p-AKT in 45.0% (36/80), 28.8% (23/80) and 18.8% (15/80) cases of DLBCL, respectively, and minimal staining in 100% (20/20) cases of RLH (P < 0.05). Compared with GCB group, the non-GCB group had higher p-STAT3 expression rate (21/57 vs. 2/23, P < 0.01). The expression of OBR was positively related with that of p-STAT3 and p-AKT in DLBCL patients (P < 0.05). Our data suggest that OBR stimulates the JAK/STAT and PI3K/AKT signaling pathway and induces the phosphorylation of STAT3 and AKT. This may be involved in carcinogenesis and prognosis of DLBCL. The specific inhibitions could interfere in the combination of leptin with OBR and obstruct the JAK/STAT and PI3K/AKT signaling pathways, which could lead to new research and treatment strategies for DLBCL treatment. 相似文献
Traumatic brain injury (TBI) is a leading cause of motor and cognitive deficits in young adults for which there is no effective therapy. The present study characterizes the protective effect of a new histone deacetylase inhibitor, Scriptaid (Sigma-Aldrich Corporation, St. Louis, MO), against injury from controlled cortical impact (CCI). Scriptaid elicited a dose-dependent decrease in lesion size at 1.5 to 5.5 mg/kg and a concomitant attenuation in motor and cognitive deficits when delivered 30 minutes postinjury in a model of moderate TBI. Comparable protection was achieved even when treatment was delayed to 12 h postinjury. Furthermore, the protection of motor and cognitive functions was long lasting, as similar improvements were detected 35 days postinjury. The efficacy of Scriptaid (Sigma-Aldrich Corporation) was manifested as an increase in surviving neurons, as well as the number/length of their processes within the CA3 region of the hippocampus and the pericontusional cortex. Consistent with other histone deacetylase inhibitors, Scriptaid treatment prevented the decrease in phospho-AKT (p-AKT) and phosphorylated phosphatase and tensin homolog deleted on chromosome 10 (p-PTEN) induced by TBI in cortical and CA3 hippocampal neurons. Notably, the p-AKT inhibitor {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 attenuated the impact of Scriptaid, providing mechanistic evidence that Scriptaid functions partly by modulating the prosurvival AKT signaling pathway. As Scriptaid offers long-lasting neuronal and behavioral protection, even when delivered 12 h after controlled cortical impact, it is an excellent new candidate for the effective clinical treatment of TBI.
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The online version of this article (doi:10.1007/s13311-012-0157-2) contains supplementary material, which is available to authorized users. 相似文献
To explore the effect of quercetin on the proliferation and apoptosis of HeLa cells, HeLa cells were incubated with quercetin at different concentrations. Cell viability was evaluated by MTT assay, cell apoptosis was detected by Annexin- V/PI double labeled cytometry and DNA ladder assay. Cell cycle was flow cytometrically determined and the morphological changes of the cells were ob- served under a fluorescence microscope after Hoechst 33258 staining and the apoptosis-related pro- teins in the HeLa cells were assessed by Western blotting. The results showed that quercetin signifi- cantly inhibited the growth of HeLa cells and induced obvious apoptosis in vitro in a time- and dose-dependent manner. Moreover, quercetin induced apoptosis of HeLa cells in cell cycle-dependent manner because quercetin could induce arrest of HeLa cells at G0/G1 phase. Quercetin treatment down-regulated the expression of the PI3K and p-Akt. In addition, quercetin could down-regulate ex- pression of bcl-2, up-regulate Bax, but exerted no effect on the overall expression of Akt. We are led to conclude that quercetin induces apoptosis via PI3k/Akt pathways, and quercetin has potential to be used as an anti-tumor agent against human cervix oancer. 相似文献
Growth arrest specific1 (Gas1) is a protein expressed during development and when cells arrest their growth. The potential of Gas1 as an adjuvant in the treatment of cancer, and its role as a tumor suppressor have also been proposed. In this work we are addressing the molecular mechanisms by which Gas1 induces cell arrest and apoptosis of cancer cells, using primary cultures of human gliomas as a model. We had previously demonstrated the structural relationship between Gas1 and the α receptors for the Glial-cell line-Derived Neurotrophic Factor (GDNF) family of ligands, and showed that Gas1 acts by inhibiting the intracellular signaling induced by GDNF. There are also reports indicating that Gas1 positively cooperates with Sonic Hedgehog (Shh) during embryonic development and in this paper we analyzed the potential interactions between Gas1 and Shh. We show that human gliomas do not express Shh, whereas GDNF and the molecular components necessary to transduce its signaling are present in human gliomas. Furthermore, the over-expression of Gas1 induces cell arrest, apoptosis and prevents the activation of Akt, a crucial mediator of survival and cellular proliferation pathways. In the present work, we present evidence demonstrating that Gas1 exerts its effects inhibiting cell growth and inducing apoptosis of glioma cells in the absence of Shh. 相似文献