Curcumin, the active chemical of the Asian spice turmeric, exhibits anticancer activity in several human cancer cell lines. We previously have proved that curcumin was a new member of the histone deacetylases (HDAC) inhibitors, while constitutive nuclear factor kappa B (NF-κ B) is believed to be a crucial event for enhanced proliferation and survival of malignant cells. Here, we investigate the effect of curcumin on the activation of NF-κ B signal molecule in Raji cells to explore its relationship with HDACs or p300/CREB binding protein (CBP). Curcumin presented striking proliferation inhibition potency on Raji cells in vitro , with the IC 50 value for 24 hr being 25 µ mol/l. Significant decreases in the amounts of p300, HDAC1 and HDAC3 were detected after treatment with curcumin. These suppressing effects were more pronounced when the administered dose increased. The protection degradation of HDAC1 and p300 by MG-132 could be partially reversed by curcumin. Furthermore, curcumin could also prevent degradation of I κ B α and inhibit nuclear translocation of the NF-κ B/p65 subunit, as well as expression of Notch 1, induced by tumour necrosis factor-α . The results suggest that the depressive effect of curcumin on NF-κ B signal transduction pathway may be mediated via the various components of the HDACs and p300/Notch 1 signal molecules, and may represent a new remedy for acute leukaemia.
Diets that may promote intestinal inflammation, based on EDIP score, are associated with increased risk of F nucleatum-positive colorectal carcinomas, but not carcinomas that do not contain these bacteria. These findings indicate that diet-induced intestinal inflammation alters the gut microbiome to contribute to colorectal carcinogenesis; nutritional interventions might be used in precision medicine and cancer prevention.
BackgroundIn locally advanced rectal cancer (LARC), preoperative short-course radiotherapy (SCRT) with delayed surgery has been shown to be as effective as long-course chemoradiotherapy, with only modest benefits. This study aimed to evaluate the efficacy and safety of preoperative SCRT combined with subsequent CAPOX (capecitabine and oxaliplatin) and the anti-PD-1 antibody camrelizumab in patients with LARC.MethodsThis was a prospective, single-arm, phase II trial. Treatment-naïve patients with histologically confirmed T3-4N0M0 or T1-4N+M0 rectal adenocarcinoma received 5×5 Gy SCRT with two subsequent 21-day cycles of CAPOX plus camrelizumab after 1 week, followed by radical surgery after 1 week. The primary endpoint was pathological complete response (pCR) rate. Biomarker analysis was performed to identify a potential predictor of pCR to treatment.ResultsFrom November 7, 2019 to September 14, 2020, 30 patients were enrolled, and 27 patients received at least one dose of CAPOX plus camrelizumab. Surgery was performed in 27 (100%) patients. The pCR (ypT0N0) rate was 48.1% (13/27), including 46.2% (12/26) for proficient mismatch repair (MMR) tumors and 100% (1/1) for deficient MMR tumors. Immune-related adverse events were all grade 1–2, with the most common being reactive cutaneous capillary endothelial proliferation (81.5%). No grade 4/5 adverse events occurred. Biomarker analysis showed patients without FGFR1–3 deletions had a better tendency for pCR.ConclusionsSCRT combined with subsequent CAPOX plus camrelizumab followed by delayed surgery showed a favorable pCR rate with good tolerance in patients with LARC, especially in the proficient MMR setting. A randomized controlled trial is ongoing to confirm these results.Trial registration numberClinicalTrials.gov identifier: NCT04231552.
PurposeTo analyse the factors associated with rapid and significant improvement in visual acuity in patients with Leber's hereditary optic neuropathy (LHON) after gene therapy and explain the theory of this improvement.MethodsWe recruited 149 patients with LHON, who underwent gene therapy, and divided them into two groups according to the absence or presence of rapid and significant visual acuity improvements within 3 days of treatment. A bivariate logistic regression model was used to analyse relevant factors including age, the period between onset and treatment, baseline values of best corrected visual acuity (BCVA), visual field index (VFI) and pretreatment average retinal nerve fibre‐layer thickness (GRNFL). The corresponding parameters for the injected and non‐injected eyes were analysed separately.ResultsThe period between onset and treatment, and pretreatment baseline BCVA was significantly associated with rapid and significant improvement in visual acuity for both, the injected and non‐injected eyes. Moreover, pretreatment baseline VFI and GRNFL were not significantly associated with rapid and significant improvement in visual acuity. Age was significantly associated with rapid and significant improvement in visual acuity of the injected eyes.ConclusionThe period between onset and treatment, and pretreatment baseline BCVA may be important predictors of rapid and significant improvement in visual acuity in patients with LHON after gene therapy.
Importance Factors affecting visual acuity prognosis after gene therapy in Leber's hereditary optic neuropathy (LHON) patients with mutation at site 11 778 are unknown. Background To analyse correlations between visual acuity prognosis and baseline characteristics of LHON after rAAV2‐ND4 gene therapy. Design Retrospective study. Participants Fifty‐three LHON patients with a mutation at site 11 778. Methods Single‐eye intravitreal injection of rAAV2‐ND4. Main Outcome Measures Sex, onset age, duration of disease, best‐corrected visual acuity (BCVA), visual field index (VFI) and mean deviation (MD) were recorded for all patients at baseline. BCVA was recorded at 1‐ and 3‐month follow‐up visits after gene therapy. Correlations between BCVA prognosis and baseline characteristics were analysed by univariate analysis. Logistic regression analysis was performed on independent factors affecting BCVA prognosis. Results Univariate analysis showed significant differences in the VFI and MD of the injected eye between BCVA improvement and non‐improvement groups after 3 months of treatment, with greater VFI and smaller absolute MD in the BCVA improvement group. Logistic regression showed that VFI and baseline BCVA were independent prognostic factors for visual acuity. The correlation between VFI and MD was statistically significant. Conclusions and Relevance VFI and baseline BCVA were correlated with the visual acuity prognosis of LHON patients receiving gene therapy, with greater baseline VFI and better baseline BCVA predicting better visual acuity prognosis. MD was strongly correlated with VFI and might be correlated with gene therapy prognosis. This finding may form a basis for predicting the efficacy of gene therapy in these patients and guiding subsequent treatment.
Suberoylanilide hydroxamic acid (SAHA), a potent pan-histone deacetylase (HDAC) inhibitor, has been clinically approved for the treatment of cutaneous T-cell lymphoma (CTCL). SAHA has also been shown to exert a variety of anticancer activities in many other types of tumors, however, few studies have been reported in large-cell lung carcinoma (LCC). Our study aimed to investigate the potential antitumor effects of SAHA on LCC cells. Here, we report that SAHA was able to inhibit the proliferation of the LCC cell line NCI-H460 in a dose- and time-dependent manner, induced cell apoptosis and G2/M cell cycle arrest, decreased AKT and ERK phosphorylation, inhibited the expression of pro-angiogenic factors (VEGF, HIF-1α) in vitro, and suppressed tumor progression in an NCI-H460 cell nude mouse xenograft model in vivo. These results indicate that SAHA can exert its strong antitumor effects in LCC patient.
Hepatic ischemia-reperfusion (I/R) injury is a serious complication in clinical practice. However, no efficient biomarkers are available for the evaluation of the severity of I/R injury. Recently, renalase has been reported to be implicated in the I/R injury of various organs. This protein is secreted into the blood in response to increased oxidative stress. To investigate the responsiveness of renalase to oxidative stress, we examined the changes of renalase in cell and mouse models. We observed a significant increase of renalase expression in HepG2 cells in a time- and dose-dependent manner when treated with H2O2. Renalase expression also increased significantly in liver tissues that underwent the hepatic I/R process. The increased renalase levels could be efficiently suppressed by antioxidants in vitro and in vivo. Furthermore, serum renalase levels were significantly increased in the mouse models and also efficiently suppressed by antioxidants treatment. The variation trends are consistent between renalase and liver enzymes in the mouse models. In conclusion, renalase is highly sensitive and responsive to oxidative stress in vitro and in vivo. Moreover, renalase can be detected in the blood. These properties make renalase a highly promising biomarker for the evaluation of the severity of hepatic I/R injury.
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