Gene Expression Profiles in Genetically Different Mice Infected with Toxoplasma gondii: ALDH1A2, BEX2, EGR2, CCL3 and PLAU

Toxoplasma gondii can modulate host cell gene expression; however, determining gene expression levels in intermediate hosts after T. gondii infection is not known much. We selected 5 genes (ALDH1A2, BEX2, CCL3, EGR2 and PLAU) and compared the mRNA expression levels in the spleen, liver, lung and small intestine of genetically different mice infected with T. gondii. ALDH1A2 mRNA expressions of both mouse strains were markedly increased at day 1-4 postinfection (PI) and then decreased, and its expressions in the spleen and lung were significantly higher in C57BL/6 mice than those of BALB/c mice. BEX2 and CCR3 mRNA expressions of both mouse strains were significantly increased from day 7 PI and peaked at day 15-30 PI (P<0.05), especially high in the spleen liver or small intestine of C57BL/6 mice. EGR2 and PLAU mRNA expressions of both mouse strains were significantly increased after infection, especially high in the spleen and liver. However, their expression patterns were varied depending on the tissue and mouse strain. Taken together, T. gondii-susceptible C57BL/6 mice expressed higher levels of these 5 genes than did T. gondii-resistant BALB/c mice, particularly in the spleen and liver. And ALDH1A2 and PLAU expressions were increased acutely, whereas BEX2, CCL3 and EGR2 expressions were increased lately. Thus, these demonstrate that host genetic factors exert a strong impact on the expression of these 5 genes and their expression patterns were varied depending on the gene or tissue

Prognostic impact of clinicopathologic parameters in stage II/III breast cancer treated with neoadjuvant docetaxel and doxorubicin chemotherapy: paradoxical features of the triple negative breast cancer

<p>Abstract</p> <p>Background</p> <p>Prognostic factors in locally advanced breast cancer treated with neoadjuvant chemotherapy differ from those of early breast cancer. The purpose of this study was to identify the clinical significance of potential predictive and prognostic factors in breast cancer patients treated by neoadjuvant chemotherapy.</p> <p>Methods</p> <p>A total of 145 stage II and III breast cancer patients received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. We examined the clinical and biological factors (ER, PR, p53, c-erbB2, bcl-2, and Ki-67) by immunohistochemistry. We analyzed clinical outcome and their correlation with clinicopathologic parameters.</p> <p>Results</p> <p>Among the clinicopathologic parameters investigated, none of the marker was correlated with response rate (RR) except triple negative phenotype. Patients with triple negative phenotype showed higher RR (83.0% in triple negative <it>vs</it>. 62.2% in non-triple negative, <it>p </it>= 0.012) and pathologic complete RR (17.0% in triple negative <it>vs</it>. 3.1% in non-triple negative, <it>p </it>= 0.005). However, relapse free survival (RFS) and overall survival (OS) were significantly shorter in triple negative breast cancer patients (<it>p </it>< 0.001, <it>p </it>= 0.021, respectively). Low histologic grade, positive hormone receptors, positive bcl-2 and low level of Ki-67 were associated with prolonged RFS. In addition, positive ER and positive bcl-2 were associated with prolonged OS. In our homogeneous patient population, initial clinical stage reflects RFS and OS more precisely than pathologic stage. In multivariate analysis, initial clinical stage was the only significant independent prognostic factor to impact on OS (hazard ratio 3.597, <it>p </it>= 0.044).</p> <p>Conclusion</p> <p>Several molecular markers provided useful predictive and prognostic information in stage II and III breast cancer patients treated with neoadjuvant docetaxel/doxorubicin chemotherapy. Triple negative phenotype was associated with shorter survival, even though it was associated with a higher response rate to neoadjuvant chemotherapy.</p

Shallow Fully Connected Neural Network Training by Forcing Linearization into Valid Region and Balancing Training Rates

A new supervisory training rule for a shallow fully connected neural network (SFCNN) is proposed in this present study. The proposed training rule is developed based on local linearization and analytical optimal solutions for linearized SFCNN. The cause of nonlinearity in neural network training is analyzed, and it is removed by local linearization. The optimal solution for the linearized SFCNN, which minimizes the cost function for the training, is analytically derived. Additionally, the training efficiency and model accuracy of the trained SFCNN are improved by keeping estimates within a valid range of the linearization. The superiority of the proposed approach is demonstrated by applying the proposed training rule to the modeling of a typical nonlinear pH process, Boston housing prices dataset, and automobile mileage per gallon dataset. The proposed training rule shows the smallest modeling error and the smallest iteration number required for convergence compared with several previous approaches from the literature for the case study

Real-time reverse transcription PCR analysis for validation of transketolase gene in hepatocellular carcinoma tissues

Hepatocellular carcinoma (HCC) is the most common malignant tumor in the adult liver, with high relapse and mortality rates despite diverse treatment modalities. In this study, expression of transketolase (TKT) and transketolase-like 1 (TKTL1) gene, coding for the rate-limiting enzyme in non-oxidative pentose phosphate pathway (PPP), was investigated as a potential prognostic factor of HCC. The expression level of TKT and TKTL1 gene was measured by real-time reverse-transcription PCR (RT-PCR) in 185 primary HCCs and 49 non-cancerous surrounding livers. TKT mRNA level was markedly elevated in HCCs compared to non-cancerous surrounding tissues (P < 0.0001). On the other hand, TKTL1 mRNA level was higher in HCCs compared to non-cancerous surrounding tissues but the difference was not statistically significant. TKT expression in tumors was significantly correlated with several clinicopathologic parameters including tumor size and Edmondson grade. Moreover, patients who expressed higher TKT mRNA levels had a significantly shorter overall survival (OS) time (P = 0.00099) and a significantly shorter disease-free survival (DFS) time (P = 0.0055). In a multivariate analysis, high TKT expression was found to be an independent prognostic factor for OS both as a discrete variable (P = 0.009) and as a continuous variable (P = 0.0068). The results of this study indicated that TKT gene expression is a significant prognostic factor for OS in HCC cases. Therefore, TKT merits further investigation regarding its role as a prognostic factor with a larger cohort of HCC patients.113sciescopuskciothe