Background Inflammation is an important hallmark of cancer. Fibrinogen and albumin are both vital factors in systemic inflammation. This study investigated the prognostic value of the fibrinogen/albumin ratio in HCC patients who underwent curative resection. Methods HCC patients (n = 151) who underwent curative resection were evaluated retrospectively. The optimal cutoff value for the fibrinogen/albumin ratio was selected by receiver operating characteristic (ROC) curve analysis. Correlations between preoperative fibrinogen/albumin ratios and clinicopathologic characteristics were analyzed by χ
2 test. The area under the receiver operating characteristic curve (AUC) was calculated to compare the prognostic value of the fibrinogen/albumin ratio with other prognostic scores (neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and albumin-bilirubin (ALBI) score). The overall survival (OS) and time to recurrence (TTR) were assessed by the log-rank test and the Cox proportional hazard regression model. Results An optimal cutoff value of the preoperative fibrinogen/albumin ratio (0.062) was determined for 151 patients who underwent curative resection for HCC via a ROC curve analysis. Fibrinogen/albumin ratio > 0.062 was significantly associated with microvascular invasion, an advanced BCLC stage, and ALBI grade. Multivariate analyses revealed that fibrinogen/albumin ratio was an independent predictor for OS (P = 0.003) and TTR (P = 0.035). The prognostic ability of fibrinogen/albumin ratio was comparable to other prognostic scores (NLR, PLR, and ALBI score) by AUC analysis. Patients with a fibrinogen/albumin ratio > 0.062 had lower 1-, 3-, and 5-year OS rates (66.0%, 41.8%, and 28.2% versus 81.9%, 69.3%, and 56.1%, resp., P < 0.001) and higher 1-, 3-, and 5-year recurrence rates (60.9%, 79.2%, and 90.5% versus 49.5%, 69.1%, and 77.1%, resp., P = 0.008) compared with patients with fibrinogen/albumin ratio ≤ 0.062. Conclusion The preoperative fibrinogen/albumin ratio is an effective prognostic factor for HCC patients who underwent curative resection. An elevated fibrinogen/albumin ratio significantly correlates with poorer survival and a higher risk of recurrence in HCC patients.
F-box and WD repeat domain-containing 7 (Fbxw7/hAgo/hCdc4/Fbw7) is a p53-dependent tumor suppressor and leads to ubiquitination-mediated suppression of several oncoproteins including c-Myc, cyclin E, Notch, c-Jun and others. Our previous study has indicated that low expression of Fbxw7 was negatively correlated with c-Myc, cyclin E and mutant-p53 in hepatocellular carcinoma (HCC) tissues. But the role and mechanisms of Fbxw7 in HCC are still unknown. Here, we investigated the function of Fbxw7 in HCC cell lines and the anti-tumor activity of recombinant human adenovirus-p53 injection (rAd-p53, Gendicine) administration in vitro and in vivo. Fbxw7-specific siRNA enhanced expression of c-Myc and cyclin E proteins and increased proliferation in cell culture. rAd-p53 inhibited tumor cell growth with Fbxw7 upregulation and c-Myc and cyclin E downregulation in vitro and a murine HCC model. This effect could be partially reverted using Fbxw7-specific siRNA. Here, we suggest that the activation of Fbxw7 by adenoviral delivery of p53 leads to increased proteasomal degradation of c-Myc and cyclin E enabling growth arrest and apoptosis. Addressing this pathway, we identified that rAd-p53 could be a potential therapeutic agent for HCC.
Background/Aims: Long non-coding RNAs (LncRNAs) have been validated to be pivotal mediators in multidrug resistance (MDR) of various cancers. This study aims to explore the roles and molecular mechanisms of linc00518 implicated in chemoresistance in breast cancer. Methods: Expressions of linc00518, miR-199a and MRP1 were evaluated by RT-qPCR or western blot. IC 50 values of adriamycin (ADR), vincristine (VCR) and paclitaxel (PTX) were determined by XTT assays and cell apoptosis was assessed by flow cytometry. Luciferase reporter and RIP assays were employed to detect the interaction of linc00518, miR-199a and MRP-1. Results: linc00518 expression increased nearly 2 fold and MRP1 level elevated about 2.5 fold in breast cancer tissues as compared to that in adjacent normal tissues. Also, almost 2 fold upregulation of linc00518 and MRP-1 expressions was observed in MCF-7 cells than in MCF-10A cells. Additionally, linc00518 level was almost 2.5 fold higher and MRP1 level was about 2 fold increased in ADR-resistant MCF-7 cells (MCF-7/ADR) than in parental cell line MCF-7. Linc00518 knockdown enhanced chemosensitivity to ADR, VCR and PTX, and boosted ADR-, VCR-and PTX-induced apoptosis in MCF-7/ADR cells. miR-199a inhibitor conferred chemoresistance to ADR, VCR and PTX in MCF-7/ADR cells, and suppressing miR-199a reversed multi-drug susceptibility induced by linc00518 knockdown. Furthermore, linc00518 could act as a molecular sponge of miR-199a to repress MRP1 expression. MRP1 depletion increased the sensitivity of MCF-7/ADR cells to ADR, VCR and PTX, and this effect was attenuated following miR-199a inhibition or linc00518 overexpression. Also, linc00518 silencing increased ADRmediated anti-tumor effect in vivo. Conclusions: linc00518 downregulation reduced MDR by regulating miR-199a/MRP1 axis in breast cancer.
The meta-analysis indicated that knee OA risk increased almost exponentially according with the increase of body mass index. Knee OA prevention will benefit from weight control.
Paeoniflorin (PF) is a monoterpene glycoside extracted from the root of Paeonia lactiflora Pall. Previous studies have demonstrated that PF inhibits the growth, invasion, and metastasis of tumors in vivo and in vitro. However, the effect of PF on hypoxia-induced epithelial–mesenchymal transition (EMT) in breast cancer cells remains unknown. Therefore, the objective of this study was to investigate the effect of PF on hypoxia-induced EMT in breast cancer cells, as well as characterize the underlying mechanism. The results presented in this study demonstrate that PF blocks the migration and invasion of breast cancer cells by repressing EMT under hypoxic conditions. PF also significantly attenuated the hypoxia-induced increase in HIF-1α level. Furthermore, PF prevented hypoxia-induced expression of phosphorylated PI3K and Akt in MDA-MB-231 cells. In conclusion, PF prevented hypoxia-induced EMT in breast cancer cells by inhibiting HIF-1α expression via modulation of PI3K/Akt signaling pathway. This finding provides evidence that PF can serve as a therapeutic agent for the treatment of breast cancer.
In this meta-analysis, we aimed to assess glycosylated hemoglobin (HbA1c) level and lower extremity amputation (LEA) risk in patients with diabetes. Systematic computerized searches of the PubMed and Web of Knowledge were performed. We compared HbA1c level between groups with LEA and without LEA by meta-analysis; we also examined the dose-response relationship between HbA1c level and LEA risk. Sixteen studies were included in the meta-analysis. Eleven studies with 43,566 patients compared HbA1c between groups with and without LEA. The mean HbA1c (%) ranged from 8.3 to 12.5 in the group with LEA and from 7.4 to 11.3 in the group without LEA. The pooled weighted mean difference was 1.110 (95% confidence interval = 0.510-1.709; Z = 3.63, P = .008). The funnel plot was symmetrical, and Begg's test (z = 0.00, P = 1.000) and Egger's test (t = -0.02, P = .984) suggested no significant publication bias. Six studies with 109,933 patients included in the dose-response meta-analysis. The LEA incidence ranged from 0.3% to 14.6% between different HbA1c levels. Dose-response meta-analysis showed statistically significant association between HbA1c and LEA risk (χ(2) = 65.51, P = .000). In linear model, the odds ratio for LEA incidence was 1.229 (95% confidence interval = 1.169-1.292) for every 1% HbA1c increase. In the spline model, the odds ratio of LEA risk increased with HbA1c levels, especially when HbA1c ranged from 5% to 9%. Our meta-analysis indicates that high level of HbA1c is an important risk factor for LEA in patients with diabetes. This evidence supports the strategy for lowering glucose levels to reduce amputation in patients with diabetes.
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