Prevalence of Aflatoxin-Associated TP53R249S Mutation in Hepatocellular Carcinoma in Hispanics in South Texas

We aimed to determine whether aflatoxin dietary exposure plays a role in the high incidence of hepatocellular carcinoma (HCC) observed among Hispanics in South Texas. We measured TP53R249S somatic mutation, hallmark of aflatoxin etiology in HCC, using droplet digital PCR and RFLP. TP53R249S mutation was detected in 3 of 41 HCC tumors from Hispanics in South Texas (7.3%). We also measured TP53R249S mutation in plasma cell-free DNA (cfDNA) from 218 HCC patients and 96 Hispanic subjects with advanced fibrosis or cirrhosis, from South Texas. The mutation was detected only in Hispanic and Asian HCC patients, and patients harboring TP53R249S mutation were significantly younger and had a shorter overall survival. The mutation was not detected in any Hispanic subject with advanced fibrosis or cirrhosis. Genes involved in cell-cycle control of chromosomal replication and in BRCA1-dependent DNA damage response were enriched in HCCs with TP53R249S mutation. The E2F1 family members, E2F1 and E2F4, were identified as upstream regulators. TP53R249S mutation was detected in 5.7% to 7.3% of Hispanics with HCC in South Texas. This mutation was associated with a younger age and worse prognosis. TP53R249S was however not detected in Hispanics in South Texas with cirrhosis or advanced fibrosis. Aflatoxin exposure may contribute to a small number of HCCs in Hispanics in South Texas, but the detection of TP53R249S mutation in plasma cfDNA is not a promising biomarker of risk assessment for HCC in subjects with cirrhosis or advanced fibrosis in this population. Cancer Prev Res; 11(2); 103-12. ©2017 AACR

Positron Emission Tomography Imaging of CD105 Expression with a 64Cu-Labeled Monoclonal Antibody: NOTA Is Superior to DOTA

Optimizing the in vivo stability of positron emission tomography (PET) tracers is of critical importance to cancer diagnosis. In the case of 64Cu-labeled monoclonal antibodies (mAb), in vivo behavior and biodistribution is critically dependent on the performance of the bifunctional chelator used to conjugate the mAb to the radiolabel. This study compared the in vivo characteristics of 64Cu-labeled TRC105 (a chimeric mAb that binds to both human and murine CD105), through two commonly used chelators: 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Flow cytometry analysis confirmed that chelator conjugation of TRC105 did not affect its CD105 binding affinity or specificity. PET imaging and biodistribution studies in 4T1 murine breast tumor-bearing mice revealed that 64Cu-NOTA-TRC105 exhibited better stability than 64Cu-DOTA-TRC105 in vivo, which resulted in significantly lower liver uptake without compromising the tumor targeting efficiency. In conclusion, this study confirmed that NOTA is a superior chelator to DOTA for PET imaging with 64Cu-labeled TRC105

Prediction of CO2 Emission in China’s Power Generation Industry with Gauss Optimized Cuckoo Search Algorithm and Wavelet Neural Network Based on STIRPAT model with Ridge Regression

Power generation industry is the key industry of carbon dioxide (CO2) emission in China. Assessing its future CO2 emissions is of great significance to the formulation and implementation of energy saving and emission reduction policies. Based on the Stochastic Impacts by Regression on Population, Affluence and Technology model (STIRPAT), the influencing factors analysis model of CO2 emission of power generation industry is established. The ridge regression (RR) method is used to estimate the historical data. In addition, a wavelet neural network (WNN) prediction model based on Cuckoo Search algorithm optimized by Gauss (GCS) is put forward to predict the factors in the STIRPAT model. Then, the predicted values are substituted into the regression model, and the CO2 emission estimation values of the power generation industry in China are obtained. It’s concluded that population, per capita Gross Domestic Product (GDP), standard coal consumption and thermal power specific gravity are the key factors affecting the CO2 emission from the power generation industry. Besides, the GCS-WNN prediction model has higher prediction accuracy, comparing with other models. Moreover, with the development of science and technology in the future, the CO2 emission growth in the power generation industry will gradually slow down according to the prediction results

Performance and emissions of a diesel engine fueled by coal-based diesel fuels and their blends with polyoxymethylene dimethyl ethers

Abstract The objective of this study was to investigate the performance and emissions of a diesel engine fueled by coal-based diesel fuels and their blends with oxygenated fuel polyoxymethylene dimethyl ethers (PODEn). First, coal-based Fischer–Tropsch (FT) diesel fuel was blended with hydrogenated diesel fuel at three volume ratios of 40%/60%, 50%/50%, and 60%/40%, denoted as T6W4, T5W5, and T4W6, respectively. Then, PODEn were added into the T4W6 fuel with the volume ratios of 10%, 20%, and 30% to evaluate its effects on the performance and emissions of a coal-based diesel engine. The results showed that the output torques and powers of the three coal-based diesel blends were slightly lower than those of the petroleum diesel fuel. The brake specific fuel consumption (BSFC) of the coal-based diesel fuels was almost the same as that of the petroleum diesel fuel. The brake thermal efficiencies (BTE) of the coal-based diesel blends were slightly lower than that of the petroleum diesel fuel, and the maximum reduction was 1.59%. The pollutant emissions of T5W5 were the closest to those of petroleum diesel fuel. The nitrogen oxides (NOx) emissions of T4W6 were lower, with a maximum decrease of 11.18% compared with the petroleum diesel. The carbon monoxide (CO) and hydrocarbon (HC) emissions of T6W4 were the highest, with maximum increases of 36.79% and 29.05%, respectively. The smoke emissions of T4W6 and T6W4 were higher than those of petroleum diesel fuel. Adding PODEn into T4W6 lowered the engine power and torque but increased the BSFC and BTE. The output torque and power of the diesel engine were further reduced when PODEn were blended with T4W6, with the maximum reductions of 17.76% and 16.96%, respectively. With an increase in the PODEn blending ratio, BSFC and BTE increased gradually, and the maximum increase in the BTE was 1.57%. Blending PODEn with the fuel effectively improved the emission characteristics of the coal-based diesel fuels. The NOx emissions increased slightly, but the emissions of HC, CO, and smoke were reduced significantly, with maximum reductions of 24.42%, 31.67%, and 82.35%, respectively

Integrin αvβ6 and transcriptional factor Ets-1 act as prognostic indicators in colorectal cancer

Background: Both transcriptional factor Ets-1 and integrin αvβ6 play an important role in the development and progression of cancer. The aim of our study was to investigate the expression of Integrin αvβ6 and Ets-1, two proteins’ correlation and their clinical significance in colorectal cancerous tissues. Results: The specimens were arranged into microarray using the immunohistochemistry method to investigate the expression of integrin αvβ6 and transcriptional factor Ets-1 in these tissues. Among the 158 tissue specimens, 36.07% were positive for αvβ6 expression, and 57.59% were positive for Ets-1 expression. There were obvious statistical differences existed regarding differentiation, N stage, M stage and TNM stage between αvβ6 and Ets-1 positively and negatively expressing tumors. The correlation analysis confirmed the expression of αvβ6 and Ets-1 were positively correlated in colorectal cancer. The Kaplan-Meier survival analysis showed that patients who were both αvβ6 and Ets-1 positive relapsed earlier than those who were both αvβ6 and Ets-1 negative; and the former group had much shorter survival time than the latter. And Cox model indicated that αvβ6 and Ets-1 were the independent prognostic factors (RR = 2.175, P = 0.012 and RR = 3.903, P < 0.001). Conclusions: The expression of αvβ6 and Ets-1 were positively correlated, and their expression degrees were associated with the differentiation, N stage, M stage and TNM stage of the tumors. Hence, the combination of αvβ6 and Ets-1 can be used as a prognostic marker in colorectal cancer, especially for the early stage

PKC promotes the migration of colon cancer cells by regulating the internalization and recycling of integrin αvβ6

Recently published studies have suggested that integrin trafficking is necessary to support cell migration, but the role of internalization and recycling of integrin αvβ6 in colon cancer cells remained unclear. In our study, we demonstrated the existence of the integrin cycle and found that inhibition of ERK2 phosphorylation by PD98059 or deletion of the ERK2 direct binding site on the β6 cytoplasmic domain could interrupt the internalization of integrin αvβ6, but had no effect on its recycling. Furthermore, integrin αvβ6 trafficking played a key role in the migration of colon cancer cells towards fibronectin. Activation of PKC significantly accelerated the internalization and recycling of integrin αvβ6, which could facilitate rapid redistribution of integrin αvβ6 and increase cell motility. When colon cancer cells became crowded, the increase in αvβ6 levels at the cell surface was not accompanied by a change in total αvβ6 expression in cell lysates. This change may be due to a redistribution of αvβ6 in cell microstructures and a rapid cellular response towards the demands of migration