All-trans retinoic acid (ATRA) is considered to be the sole clinically-useful differentiating agent in the treatment of acute myeloid leukemia (AML). However, ATRA has been effective only in acute promyelocytic leukemia (APL) but not other subtypes of AML. Therefore, discovering strategies to sensitize cells to ATRA may lead to the development of ATRA-based treatments in non-APL AML patients. In the present study, a clinically-achievable concentration of enzastaurin enhanced ATRA-induced differentiation in AML cell lines, HL-60 and U937 as well as non-APL AML primary cells. Furthermore, it also restored ATRA sensitivity in ATRA-resistant cell line, HL-60Res. Mechanistically, in all these cell lines, enzastaurin-ATRA (enz-ATRA) co-treatment enhanced the protein levels of PU.1, CCAAT/enhancer-binding protein β (C/EBPβ) and C/EBPε. LY2090314 in vitro The activity of protein kinase C β (PKCβ) was suppressed by enz-ATRA treatment in HL-60 and HL-60Res cells. However, another PKCβ-selective inhibitor mimicked the cellular and molecular effects of enzastaurin only in HL-60 cells. Furthermore, in U937 cells, enz-ATRA activated MEK and ERK, and a MEK-specific inhibitor suppressed enz-ATRA-triggered differentiation and reduced the protein levels of PU.1, C/EBPβ and C/EBPε. Enz-ATRA activated Akt in HL-60 and HL-60Res cells. However, an Akt inhibitor blocked enz-ATRA-triggered differentiation and restored the protein levels of PU.1, C/EBPβ and C/EBPε only in HL-60Res cells. Therefore, PKCβ inhibition, MEK/ERK and Akt activation were involved in enz-ATRA-induced differentiation in HL-60, U937 and HL-60Res cells, respectively, via modulation of the protein levels of C/EBPβ, C/EBPε and PU.1. Taken together, our findings may help to guide novel therapeutic strategies for AML patients.
To investigate the expression levels of hypoxia-inducible factor-1α (HIF-1α) and C-reactive protein (CRP) in patients with ulcerative colitis and correlations of HIF-1α and CRP levels with disease severity.
A total of 82 patients with confirmed ulcerative colitis were enrolled in this study and according to the disease severity grading, these patients were assigned into three groups mild group (n=25), moderate group (n=31) and severe group (n=26). And other 30 patients without ulcerative colitis as demonstrated by colonoscopy examination were enrolled in control group in the same period. HIF-1α and CRP levels were detected by ELISA and Real-time PCR and compared among different groups. Pearson's correlation analysis was performed to evaluate the correlations of HIF-1α and CRP levels with disease severity. Logistic regression analysis was used to explore risk factors of disease severity in patients with ulcerative colitis.
The expression levels of HIF-1α and CRP in ulcerative colitis group were significay correlated with the progression of ulcerative colitis, indicating that the detection of HIF-1α and CRP expression could be used for predicting the disease severity.Bone regeneration has always been a hot topic for orthopedic surgeons. The role of polydopamine coating in promoting bone regeneration has attracted much attention. Static magnetic field (SMF) is considered an effective and noninvasive treatment for enhancing bone regeneration. However, the effect of polydopamine combined with SMF on bone regeneration on scaffolds is not clear. The aim of this study was to investigate the effects and potential mechanism of polydopamine coating combined with SMF on bone regeneration in three-dimensional printed scaffolds. The polydopamine coating (pTi group) was applied onto porous Ti6Al4V scaffolds (Ti group). Surface characterization was performed by scanning electron microscopy. The 100 mT SMF environment (pTi-SMF group) was established to enhance osteogenic differentiation of human bone-derived mesenchymal stem cells (hBMSCs) on polydopamine coating scaffolds. The cell viability and proliferation were significantly enhanced in the SMF environment (pTi-SMF vs. Ti P=0.005). ds could be enhanced by SMF stimulation by upregulation of the BMP-Smads signaling pathway.
Engulfment and cell motility 1 (ELMO1) protein has been implicated in phagocytosis of apoptotic cells, cell migration, neurite outgrowth, cancer cell invasion and metastasis, and poor prognosis in various cancers. We investigated the role of ELMO1 in mediating the oncogenic behavior of gastric cancer (GC) cells. We also investigated the correlation between expression of ELMO1 in GC tissues and various clinicopathological parameters.
We studied the impact of ELMO1 on tumor cell behavior using the pcDNA-myc vector and small interfering RNA in AGS and SNU1750 GC cell lines. We performed western blotting and immunohistochemistry to investigate the expression of ELMO1 in GC cells and tissues.
ELMO1 overexpression inhibited apoptosis via the modulation of PARP, caspase-3 and caspase-7 in GC cells. ELMO1 overexpression led to significant increase in the number of migrating and invading GC cells. The expression of E-cadherin decreased and that of Snail increased in GC cells upon ELMO1 overexpression. Phosphorylation of PI3K/Akt and GSK-3β was increased and that of β-catenin was decreased upon ELMO1 overexpression in GC cells. These results were reversed after ELMO1 knockdown. ELMO1 expression was significantly associated with tumor size, cancer stage, lymph node metastasis and survival. ELMO1-positive tumors had significantly higher mean of Ki-67 labeling index than ELMO1-negative tumors. There was no significant relationship between ELMO1 expression and the mean value of the apoptotic index.
Our results indicate that ELMO1 promotes tumor progression by modulating tumor cell survival in human GC.
Our results indicate that ELMO1 promotes tumor progression by modulating tumor cell survival in human GC.
Cancer/testis antigens (CTAs) are attractive therapeutic targets for tumor immunotherapy due to their restrictive expression in normal testis but excessive in majority of tumor types. ACTL8, CTCFL, OIP5 and XAGE3 are members of the CTAs family. Currently, the data of ACTL8, CTCFL, OIP5 and XAGE3 expression in glioma is limited.
ACTL8, CTCFL, OIP5 and XAGE3 mRAN and protein expressions were detected in 108 glioma samples by Reverse Transcriptase-PCR (RT-PCR) and immunohistochemistry and the correlations between their expressions and clinical indexes were analyzed. Furthermore, their clinical significance on glioma prognosis was determined by follow-up data.
The mRNA positive rate of ACTL8, CTCFL, OIP5 and XAGE3 was 15.74% (17/108), 22.22% (24/108), 13.89% (15/108) and 37.96% (41/108), respectively. At least one CTA mRNA was expressed by 61.11% of glioma tissues, while 2 or more by 29.63%. For protein expression, the positive rate of them was 21.30% (23/108), 34.26% (37/108), 19.44% (21/108) and 23.15% (25/108), respectively.LY2090314 in vitro
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