Zinc-finger protein 750 mitigates malignant biological behavior of oral CSC-like cells enriched from parental CAL-27 cells.

Oral squamous cell carcinoma (OSCC) is the most commonly occurring oral malignancy. Cancer stem cells (CSCs) are known to be responsible for cancer recurrence and metastasis. Zinc-finger protein 750 (ZNF750) has been reported to inhibit OSCC cell proliferation and invasion. The present study aimed to elucidate the role of ZNF750 in the inhibition of the renewal ability of CSCs derived from the OSCC cell line, CAL-27. The effects of ZNF750 on CSC-like properties were examined using aldehyde dehydrogenase (ALDH), tumor sphere formation and colony formation assays. Reverse transcription-quantitative PCR and western blotting were performed to detect the expression levels of octamer-binding transcription factor 4, sex-determining region Y-box 2, the enhancer of zeste homolog 2 (Ezh2), embryonic ectoderm development (EED) and SUZ12 polycomb repressive complex 2 subunit (SUZ12), and for the identification of genes associated with metastasis. ZNF750 effectively attenuated CSC-like cell self-renewal abilities; ZNF750 decreased the ALDH-positive cell population, tumor sphere and colony formation abilities, cell viability and stemness factors. Furthermore, the expression levels of Ezh2, EED and SUZ12 were decreased by ZNF750. ZNF750 inhibited MMP1, 3, 9 and 13 expression levels, and decreased the cell invasion and migratory abilities. Moreover, the expression of tissue inhibitors of matrix metalloproteinases-1 was increased by ZNF750. However, opposite effects were observed following the knockdown of the ZNF750 gene. Overall, the present study demonstrated that ZNF750 has the potential to inhibit the renewal of CSC-like cells enriched from parental CAL-27 cells.

Whole-Genome Methylation Analysis Revealed ART-Specific DNA Methylation Pattern of Neuro- and Immune-System Pathways in Chinese Human Neonates.

The DNA methylation of human offspring can change due to the use of assisted reproductive technology (ART). In order to find the differentially methylated regions (DMRs) in ART newborns, cord blood maternal cell contamination and parent DNA methylation background, which will add noise to the real difference, must be removed. We analyzed newborns' heel blood from six families to identify the DMRs between ART and natural pregnancy newborns, and the genetic model of methylation was explored, meanwhile we analyzed 32 samples of umbilical cord blood of infants born with ART and those of normal pregnancy to confirm which differences are consistent with cord blood data. The DNA methylation level was lower in ART-assisted offspring at the whole genome-wide level. Differentially methylated sites, DMRs, and cord blood differentially expressed genes were enriched in the important pathways of the immune system and nervous system, the genetic patterns of DNA methylation could be changed in the ART group. A total of three imprinted genes and 28 housekeeping genes which were involved in the nervous and immune systems were significant different between the two groups, six of them were detected both in heel blood and cord blood. We concluded that there is an ART-specific DNA methylation pattern involved in neuro- and immune-system pathways of human ART neonates, providing an epigenetic basis for the potential long-term health risks in ART-conceived neonates.

ZNF750 exerted its Antitumor Action in Oral Squamous Cell Carcinoma by regulating E2F2.

Cell cycle activator E2F transcription factor 2 (E2F2) play a key role in tumor development and metastasis. Previous RNA sequence analysis (GSE134835) revealed E2F2 was significantly reduced by Zinc-finger protein 750 (ZNF750) in oral squamous cell carcinoma (OSCC). This study was aimed to determine the involvement of E2F2 in antitumor action of ZNF750. The nude mouse xenograft model was established by subcutaneously injection of stable cell line CAL-27oeZNF750 or CAL-27shZNF750. Xenograft tumor volume and tumor weight was measured. The expression of E2F2, transcriptional repressors such as enhancer of zeste 2 (Ezh2), PHD finger protein 19 (PHF19), and the genes related to cell proliferation or metastasis was studied in vivo or in vitro. Luciferase assay was performed to investigate regulation effect of ZNF750 on E2F2 luciferase activity. The involvement of E2F2 in the antitumor action of ZNF750 was studied by cotransduced ZNF750 with E2F2 lentivirus. The tumor growth and metastasis was repressed by ZNF750 manifested by reduced tumor size, tumor weight and the genes related to cell proliferation and metastasis. However, all of these were reversed by knockdown of the ZNF750 gene. Furthermore, E2F2 luciferase activity was inhibited by ZNF750. E2F2 partly blocked the antitumor action of ZNF750 manifested by increased self-renewal, invasion, migration, elevated Ezh2 and MMP13 protein expression in ZNF750 + E2F2 groups. However, silenced E2F2 further enhanced the antitumor action of ZNF750. ZNF750 depressed E2F2 activity and played a critical role in regulating transcriptional repressors for inhibiting the OSCC growth and metastasis in OSCC.

Correlation analysis between metabolic tumor burden measured by positron emission tomography/computed tomography and the 2015 World Health Organization classification of lung adenocarcinoma, with a risk prediction model of tumor spread through air spaces.

BACKGROUND: Tumor spread through air spaces (STAS) is an important pattern of invasion and impacts the frequency and location of recurrence. The objective was to assess the correlation between metabolic tumor burden of positron emission tomography/computed tomography (PET/CT) and 2015 World Health Organization (WHO) classification of lung adenocarcinoma, and to establish a risk prediction model of STAS. METHODS: We reviewed 127 consecutive patients. The SUVmax, SUVmean, SUVpeak, MTV, TLG, diameter, and CTV were measured. All risk factors were analyzed by multivariate logistic regression analysis; regression coefficients and odds ratios were calculated for independent risk factors. A STAS risk prediction model was created using the regression coefficients to determine the predictive probability (PP). RESULTS: The nodule types and SUV were significantly correlated with 2015 WHO pathological categories (P<0.001). Most of (83.3%) the lepidic predominant adenocarcinoma (LPA) appeared as non-solid or part-solid nodules with the lowest SUV (P<0.05). There was a significant difference in STAS distribution among different nodule types (P=0.000). STAS was significantly correlated with SUVmax (P=0.000), SUVmean (P=0.000), SUVpeak (P=0.000), TLG (P=0.001), and diameter (P=0.044). The risk prediction model of STAS was established. The PP of STAS and the incidence of STAS were analyzed using the ROC curve (AUC =0.759, P=0.000). The sensitivity, specificity, and accuracy of the predictive model for STAS were 47.1%, 88.6%, and 71.1%, respectively. CONCLUSIONS: The LPA appeared as non-solid nodule with low SUV without STAS has a good prognosis. SUV and TLG are valuable predictive indices in the prediction of STAS. The predictive model developed in predicting the incidence of STAS has good specificity and accuracy.

Regioselective and oxidant-free sulfinylation of indoles and pyrroles with sulfinamides.

An unexpected time-controlled highly selective C3- or C2-sulfinylation of pyrroles with sulfinamides is reported for the first time. The sulfinylation of indoles with sulfinamides using this protocol is oxidant-free and can be performed under obviously more feasible conditions (1.2 equiv. of indoles, 10 min) in comparison with the precedent procedure (3-20 equiv. of indoles, 16-18 h, ammonium persulfate as oxidant, hv). A variety of functional groups were tolerated, and various C2-thioindoles and C2/3-thiopyrroles were obtained in moderate to excellent yields.

Surgery of primary non-small cell lung cancer with oligometastasis: analysis of 172 cases.

BACKGROUND: Previous studies have demonstrated that survival of patients with non-small cell lung cancer (NSCLC) with oligometastasis may benefit from local treatment. The purpose of this study was to compare the efficacy of local surgical treatment with systematic chemoradiotherapy in NSCLC with oligometastasis. METHODS: Data from a total of 172 patients with NSCLC with oligometastasis were collected at our Cancer Hospital from January 2006 to December 2016. The patients were divided into two groups: group A (82 cases) underwent primary surgical treatment and adjuvant chemotherapy was performed after operation, while group B (90 cases) received systematic chemotherapy and local radiotherapy. The median survival time (MST) and the 5-year survival rate of the two groups were compared and analyzed. The effects of various pathological types, surgical methods of the primary tumors and the site of oligometastasis were also analyzed. RESULTS: The MSTs in groups A and group B were 48 months and 18 months, respectively, and the 5-year survival rates were 21.1% and 7.6%, respectively (P<0.05). In group A, the survival rates were higher in patients with adrenal metastasis than patients with metastasis in the brain, bone, the liver or in other oligometastatic patients (P<0.05). There was no significant difference in the survival rate among the various pathological types or surgical methods of primary tumors (P>0.05). CONCLUSIONS: Local surgical treatment of primary lesions in NSCLC significantly prolonged overall survival and 5-year survival rates of patients with NSCLC with oligometastasis.

Prognostic value of metabolic variables of [18F]FDG PET/CT in surgically resected stage I lung adenocarcinoma.

The objective of this study was to assess the prognostic value of metabolic tumor burden measured by positron emission tomography/computed tomography (PET/CT) in patients with stage I lung adenocarcinoma.We reviewed 127 consecutive patients with pathologically proven stage I lung adenocarcinoma who underwent pretreatment [18F]FDG PET/CT scans in our hospital from 2005 June to 2012 June. The maximum, mean, and peak standardized uptake value (SUVmax, SUVmean, and SUVpeak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and computed tomography volume (CTV) were measured. The Kaplan-Meier and Cox proportional hazards model were used with age, gender, TNM stage, clinical stage, histological grade, nodule type, tumor size, and metabolic parameters to predict progression-free survival (PFS). The cut-off point was determined through receiver-operating characteristic curve.In univariate analysis, the histological grade, nodule type, diameter (cut-off value of 2.0 cm), CTV (6.56 cm), SUVmax (3.25 g/mL), SUVmean (1.58 g/mL), SUVpeak (1.84 g/mL), MTV (4.80 cm), and TLG (10.40) were significantly associated with PFS (all P value < .05). Patients with poorly differentiated adenocarcinoma, solid nodule type, large size, and high metabolic tumor burden were associated with poor prognosis. In multivariate analysis, only histological grade was independent prognostic factors for progression with a P value of .005 (RR, 0.355; 95% CI, 0.173-0.728). Among 5 PET/CT metabolic parameters, only MTV was independent prognostic factors for progression with a P value of .031 (RR, 1.118; 95% CI, 1.010-1.237).Histological grade was an independent predictor for progression in patients with stage I lung adenocarcinoma. Among 5 PET/CT metabolic parameters, only MTV was an independent predictor for progression.

Comparison of different automated lesion delineation methods for metabolic tumor volume of 18F-FDG PET/CT in patients with stage I lung adenocarcinoma.

The aim of the study was to investigate the suitable segmentation method in small, low uptake and heterogeneous nodules of stage I lung adenocarcinoma.133 stage I lung adenocarcinoma patients with F-FDG PET/CT scans were enrolled in this retrospective study. All lesions were divided into different groups according to nodule density, nodule size, and the maximum standard uptake value (SUVmax) level. Four different PET segmentation methods were performed, including percentage threshold of SUVmax (T42% and T42% × RC), gradient-based threshold (adaptive iterative algorithm, AT-AIA), and background-related threshold (adaptive thresholding at 40% SUVmax, AT40%) approaches. The MTVs were evaluated and compared with CT volume (CTV). Percentage volume error (%VE) compared to CTV was calculated and the correlations between MTVs and CTV were analyzed.AT-AIA had the highest accuracy in large, high uptake, and solid nodules (72.5%, 72.4%, and 65.6%, respectively). AT40% had the highest accuracy in small, low uptake and nonsolid nodules (56.6%, 56.1%, and 62.6%, respectively). In part-solid nodules, the accuracy of AT-AIA (60.0%) and AT40% (56.7%) were higher than that of T42% and T42% × RC. The MTV of AT-AIA was in excellent correlation with the CTV in solid nodules (R = 0.831, P < .001) and in high uptake nodules (R = 0.830, P < .001). The MTV of AT40% was in good correlation with the CTV in nonsolid nodules (R = 0.686, P = .003) and in part-solid nodules (R = 0.731, P < .001).AT40% showed best performance in small, low uptake, nonsolid and part-solid lesions. AT-AIA was suitable for large, high uptake, and solid lesions.

Zileuton reduces inflammatory reaction and brain damage following permanent cerebral ischemia in rats.

5-Lipoxygenase inhibitor zileuton has been demonstrated to attenuate ischemic brain damage in rats of permanent focal cerebral ischemia in previous work. To further investigate the mechanism underlying zileuton's neuroprotection, adult male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO), then received treatment with zileuton or vehicle after the onset of ischemia. Neurological deficit, cerebral infarction, and morphological characteristic were measured 6 and 24 h after MCAO. The enzymatic activity of myeloperoxidase (MPO) was assessed 6 and 24 h after MCAO and the lipid peroxidation levels were evaluated by malondialdehyde assay. Expression of nuclear factor-kappa B (NF-kappaB) p65 in rat brain was detected by immunohistochemistry and Western blot. Expression of inducible nitric oxide synthase (iNOS) in rat brain was determined by RT-PCR and Western blot. Nitric oxide production in rat brain was also measured 24 h after MCAO. The concentration of TNF-alpha and IL-1beta in serum were detected by ELISA. Zileuton significantly reduced neurological deficit scores, cerebral infarct volume, MPO activity, and the lipid peroxidation levels. It also inhibited the expression of NF-kappaB and decreased the expression and activity of iNOS in rat brain. In addition, zileuton attenuated the release of TNF-alpha and IL-1beta in serum. Our results suggest that zileuton reduces inflammatory reaction and brain damage in a rat model of permanent focal cerebral ischemia. The neuroprotective effect of zileuton in cerebral ischemia might be associated with the inhibition of inflammatory reaction.

[The aquation of oxaliplatin and the effect of acid].

AIM: To investigate the aquation of oxaliplatin in aqueous solution at different temperatures and gain the kinetic data. METHODS: Electronic conductometry and high performance liquid chromatography (HPLC) were used to measure the oxaliplatin content in the reaction systems at different time. RESULTS: The aquation of oxaliplatin followed a pseudo-first-order rate law. In the absence of H+, the observed rate constant kobs was 7.76 x 10(-6).min-1 and the half life t1/2 was 62 days at 25 degrees C. In the presence of H+, the aquation could be accelerated by H+ according to the equation kobs = (2.61 + 21.9 [H+]) x 10(-4).min-1. The mechanism of aquation has also been proposed in this paper. From the mechanism, the rate of aquation following to r = (k1 k2) [l-OHP]/k-1 in the absence of H+ and r = (k1 + K0k3 [H+]) [l-OHP] in the presence of H+ have been deduced, which were in perfect agreement with the experimental results. CONCLUSION: In the absence of H+, the aqueous solution of oxaliplatin is stable, which meets to the request of clinical.