Hypomethylation-driven overexpression of HJURP promotes progression of hepatocellular carcinoma and is associated with poor prognosis.

Our previous studies have initially identified HJURP, which encodes a Holliday junction recognizing protein, as a hepatocellular carcinoma (HCC) susceptibility gene. In this report, we showed that the HJURP is highly expressed in HCC tissues compared to adjacent normal tissues. Overexpression of HJURP in HCC tissues is mainly due to the hypomethylation of HJURP promoter region. Clinically, high expression of HJURP is significantly associated with poor overall survival and disease-free survival of patients with HCC, as well as in multiple other types of cancer. Gain- and loss-of functional studies demonstrated that HJURP promotes HCC cell proliferation, clone formation, migration and invasion. Additionally, HJURP enhances HCC tumorigenesis via reducing G0/G1 arrest and apoptosis. Mechanistically, by gene set enrichment analysis (GSEA) analysis, HJURP was identified as a modulator involved in CENPA-mediated centromere maintenance. Our results provide evidence of HJURP as an important oncogene that promotes HCC progression, and the HJURP pathway may be a potential target for the treatment of HCC.

Synthetic MRI and diffusion-weighted imaging for differentiating nasopharyngeal lymphoma from nasopharyngeal carcinoma: combination with morphological features.

OBJECTIVES: To investigate the feasibility of synthetic MRI (syMRI), diffusion-weighted imaging (DWI), and their combination with morphological features for differentiating nasopharyngeal lymphoma (NPL) from nasopharyngeal carcinoma (NPC). METHODS: Sixty-nine patients with nasopharyngeal tumours (NPL, n = 22; NPC, n = 47) who underwent syMRI and DWI were retrospectively enrolled between October 2020 and May 2022. syMRI and DWI quantitative parameters (T1, T2, PD, ADC) and morphological features were obtained. Diagnostic performance was assessed by independent sample t-test, chi-square test, logistic regression analysis, receiver operating characteristic curve (ROC), and DeLong test. RESULTS: NPL has significantly lower T2, PD, and ADC values compared to NPC (all P < .05), whereas no significant difference was found in T1 value between these two entities (P > .05). The morphological features of tumour type, skull-base involvement, Waldeyer ring involvement, and lymph nodes involvement region were significantly different between NPL and NPC (all P < .05). The syMRI (T2 + PD) model has better diagnostic efficacy, with AUC, sensitivity, specificity, and accuracy of 0.875, 77.27%, 89.36%, and 85.51%. Compared with syMRI model, syMRI + Morph (PD + Waldeyer ring involvement + lymph nodes involvement region), syMRI + DWI (T2 + PD + ADC), and syMRI + DWI + Morph (PD + ADC + skull-base involvement + Waldeyer ring involvement) models can further improve the diagnostic efficiency (all P < .05). Furthermore, syMRI + DWI + Morph model has excellent diagnostic performance, with AUC, sensitivity, specificity, and accuracy of 0.986, 95.47%, 97.87%, and 97.10%, respectively. CONCLUSION: syMRI and DWI quantitative parameters were helpful in discriminating NPL from NPC. syMRI + DWI + Morph model has the excellent diagnostic efficiency in differentiating these two entities. ADVANCES IN KNOWLEDGE: syMRI + DWI + morphological feature method can differentiate NPL from NPC with excellent diagnostic performance.

Phase II study of apatinib plus exemestane in estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer.

PURPOSE: Apatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR)-2. This study was conducted to assess the efficacy and safety of apatinib combined with exemestane in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). METHODS: This single-center, single-arm phase II study enrolled patients with ER+/HER2- MBC progressed on previous letrozole or anastrozole. Stratified analysis was performed according to the number of chemotherapy regimens for metastatic disease. The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS) and toxicity. Patients received apatinib at a starting dose of 500 mg/d and exemestane 25 mg/d on days 1-28 of each 4-week cycle. RESULTS: Thirty patients were enrolled with median four prior anticancer therapies. Eighty percent of patients received chemotherapy for metastatic disease. The median PFS (mPFS) and OS were 5.6 (95%CI: 4.3-6.9) months and 15.7 (95% CI: 9.7-21.7) months, respectively. The ORR, DCR, and CBR were 21.4%, 71.4%, and 46.4%, respectively. Patients with 0-1 line chemotherapy for MBC showed a slightly longer mPFS compared to those with ≥2 lines chemotherapy (mPFS: 6.4 months vs 4.8 months, P = .090). Most of the AEs were grade 1/2. One patient (3.3%) who suffered bone marrow metastases experienced grade 4 thrombocytopenia, and 14 experienced grade 3 AEs. Fifty percent of patients were given reduced dose for apatinib. CONCLUSIONS: Apatinib plus exemestane exhibited objective efficacy in patients with ER+/HER2- MBC who have failed multiple lines of treatment. The AEs of apatinib required close monitoring and most of patients were well tolerated.

Efficacy and safety of continuous infusion of Rh-endostatin combined with platinum-based chemotherapy for advanced triple-negative breast cancer.

BACKGROUND: This study aimed to prospectively evaluate and investigate the efficacy and safety of recombinant human endostatin (Rh-endostatin) combined with platinum-based regimens for advanced triple-negative breast cancer (TNBC) patients. METHODS: This study was a prospective, single-arm, single-center, open-label trial. From January 2017 to August 2019, 21 women aged 18-70 years with histologically confirmed advanced TNBC were enrolled. Rh-endostatin at 30 mg/d was continuously pumped for 7 days and used synchronously with the chemotherapy cycle. The primary endpoint of this study was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS), and toxicity. RESULTS: The median PFS (mPFS) was 8.8 months (95% CI: 7.2-10.4 months), and the median OS was 13.3 months (95% CI: 11.6-15.0 months). The ORR and CBR for the whole population were 47.6% and 52.4%, respectively. Patients sensitive to anthracycline and taxane drugs showed a significantly longer mPFS compared to those who were resistant to anthracycline and taxane drugs (mPFS: 8.8 vs. 5.3 months, P=0.038). For patients who received first- and second-line therapy or beyond, the mPFS was 8.8 and 5.3 months, respectively, with a significant difference (P=0.025). No statistically significant differences in the mPFS between pemetrexed combined with platinum and gemcitabine/taxanes combined with platinum were observed. The most common grade 3-4 hematologic toxicities were neutropenia (14.3%) and anemia (14.3%). One patient (4.8%) experienced febrile neutropenia. No grade 3-4 non-hematologic toxicities were observed, and no treatment-related deaths were reported in this study. CONCLUSIONS: This study revealed that Rh-endostatin might enhance the antitumor effects of platinum-based chemotherapy for advanced TNBC patients with well-tolerated toxicities, which may provide a new basis and novel idea for the treatment of TNBC. However, further investigations and validation of its long-term efficacy and toxicity are warranted in the future.

Mathematical model analysis of Fenton oxidation of landfill leachate.

The treatment of concentrated landfill leachate rejected from reverse osmosis (RO) with Fenton process was studied, and the system model was developed through the examination of reaction kinetics. The leachate is typically non-biodegradable with low BOD(5)/COD ratio 0.01. The oxidation reactions of Fenton process was found to be a two-stage process, where a fast initial reaction (H(2)O(2)/Fe(2+)) was followed by a much slower one (H(2)O(2)/Fe(3+)). A simple and more accurate mathematics model based on COD and TOC removals has been derived successfully to describe the two-stage reaction kinetics. The two corresponding parameters involved in this model have been identified as the initial reaction rate and the maximum oxidation removal efficiency, respectively. It was found to be very useful for evaluating the performance of Fenton system and/or for process design using the two parameters under different experimental conditions.

Modeling physical and oxidative removal properties of Fenton process for treatment of landfill leachate using response surface methodology (RSM).

In this study, the Fenton process was found to be successful to treat landfill leachate rejected after reverses osmose treatment. Central composite design (CCD) and response surface method (RSM) were applied to evaluate and optimize the interactive effects of three operating variables, initial pH and dosages of H(2)O(2) and Fe(2+) on physical and oxidative performances of Fenton process. Six dependent parameters such as overall chemical oxygen demand (COD) removal, COD removals of oxidation and coagulation, mineralization, humic substances (HS) removal and sludge volume ratio (SVR) were either directly measured or calculated as responses. According to analysis of variances (ANOVA) results, six proposed models could be used to navigate the design space with high regression coefficient R(2) varied from 0.9489 to 0.9988. It was found that initial pH, H(2)O(2) and Fe(2+) dosage had significant effects on the overall COD removal, mineralization and HS removal due to their respective effects on the oxidation and coagulation removals. Synergies effect of oxidation and coagulation during Fenton process controlled the treatment. The visual search of overlaying critical response contours plot was demonstrated. The results indicated the optimum conditions to be 3.64 of initial pH, 100 mM of Fe(2+) and 240 mM of H(2)O(2) dosage, respectively. The experimental data and model predictions agreed well. The overall COD removal, COD removals of oxidation and coagulation, mineralization, HS removal and SVR of 71.81%, 46.22%, 25.80%, 63.81%, 91.53% and 3.50 ml/mM were demonstrated.

Modeling the oxidation kinetics of Fenton's process on the degradation of humic acid.

The degradation of humic acid (HA) was carried out in the presence of the Fenton reagent. The experiments demonstrated that HA was removed by oxidation and coagulation. Moreover, the oxidation occurred mainly at the first 60 min and predominated the HA removal efficiency. A new kinetic model was established according to the generally accepted mechanism of high active OH oxidation in order to well describe the Fenton oxidation reaction in HA aqueous solution. The model embraced two key operating factors affecting the HA degradation in Fenton process, including the dosages of hydrogen peroxide and ferrous ion. The experimental data were fitted by using the most commonly used first- and the second-order reaction models and the new model, respectively. The goodness of fittings demonstrated that the new model could better fit the experimental data than the other two models, which indicated that this analytical model could better describe the kinetics of Fenton reaction mathematically and chemically. Results indicated that the oxidation rate and removal efficiency were strongly dependent on initial pH, initial concentration of Fenton reagents, initial HA concentration and reaction temperature. The experiments demonstrated that hydrogen peroxide and ferrous ion would approach their saturated value with increasing dosage.

[Removal of humic acids by oxidation and coagulation during Fenton treatment].

Simulated high concentration humic acids (HA) wastewater was treated by Fenton process. The influence of reaction time, initial pH, H2O2 and Fe2+ dosage on the reduction results of COD, TOC, UV254, A400 are presented. The changes of mean oxidation state (eta), A465/A665, the ratio of COD removal by oxidation to that by coagulation (phi) and Zeta potential (zeta) were used to evaluate the roles of oxidation and coagulation in reducing HA during Fenton treatment. The results demonstrate that Fenton's reagent can effectively degrade HA under a wide initial pH range (2.0-5.0), simultaneously the absorbance decrease in 400 nm was higher (from 78.2% to 94.5%) than that in 254 nm (from 75.6% to 88.4%) and the COD removal (from 50.8% to 62.5%) is higher than TOC removal (from 31.2% to 35.1%) in 2 h reaction time. The amount of HA is removed by both oxidation and coagulation. Oxidation played a primary role in removal of HA at the beginning of Fenton reaction. The large molecular weight component of HA appears to be easily degraded and the formations of low molecular persistent organic intermediate compounds are difficult to be mineralized. The COD removal efficiency by oxidation decreases over the ferrous dosage of 0.08 mol/L. Furthermore, the results reveal that HA removal by coagulation was reduced mainly by charge neutralization as well as adsorption bridge building. Results highlight the role of oxidation in controlling the efficiency of COD removal by coagulation, so high COD(oxid) may cause relatively low COD(coag). Meanwhile, ferrous dosage greatly influences COD removal by coagulation at high peroxide dosages over 0.2 mol/L.

[Kinetics of humic substances oxidation degradation by Fenton's reagent].

Humic substances (HS) oxidation degradation by Fenton's reagent was kinetically investigated in this study. HS was removed by both oxidation and coagulation during Fenton treatment. Moreover, initial pH, the dosage of Fenton's reagent and initial concentration of HS had a significant impact on HS oxidation rate and the oxidation mainly occurred at the first 60 min of reaction time. The empirical kinetic equation for HS oxidation by Fenton's reagent under the conditions of 308 K of temperature, 4.0 of pH, 5-40 mmol x L(-1) of Fe2+, 40-120 mmol x L(-1) of H2O2, 250-1 000 mg x L(-1) of HS, could be described using a kinetic model, which was fitted very well with the experimental data. The overall reaction order is 2.34. The lower activation energy of 14.9 kJ x mol(-1) shows that Fenton reaction can be initiated easily. The reaction order of H2O2 (0.86) is higher than that of Fe2+ (0.47), which indicates that the effect of initial H2O2 concentration is greater than that of Fe2+ on the oxidation degradation of HS by Fenton process.