Clinical trial evaluating efficacy and safety of pemetrexed based chemotherapy regimen versus ramucirumab plus erlotinib in Chinese patients with lung cancer: A preliminary investigation.

To carry out a preliminary clinical trial to compare the effectiveness and safety of pemetrexed based chemotherapy regimen in combination of cisplatin versus ramucirumab plus erlotinib in Chinese patients with metastatic non-small-cell lung cancer (NSCLC). Patients with confirmed diagnosis of NSCLC were randomly (1:1 ratio) grouped and treated intravenously with a mixture of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) plus Best Supportive Care (BSC), or ramucirumab (8 mg/kg) intravenously (IV) + erlotinib 25 mg/day. Overall survival (OS), overall response rate (ORR), progression free survival (PFS), and the safety were assessed. Pemetrexed based chemotherapy regimen in combination of cisplatin showed significantly higher OS (14.4 months vs. 10.47 months, p<0.05) and PFS (9.5 months vs. 5.1 months) than ramucirumab plus erlotinib. Objective response was also favorable in the patients treated with pemetrexed based chemotherapy regimen, when compared with those given ramucirumab plus erlotinib. Pemetrexed based chemotherapy regimen found more effective to ramucirumab plus erlotinib in improving OS, PFS and ORR, and it offers greater clinical benefits than ramucirumab plus erlotinib in Chinese NSCLC patients. Pemetrexed based chemotherapy regimen in combination of cisplatin appears to be better choice of drug for the treatment of Chinese patients with advanced stage of lung cancer.

Methods of forward feature selection based on the aggregation of classifiers generated by single attribute.

Compared to backward feature selection (BFS) method in gene expression data analysis, forward feature selection (FFS) method can obtain an expected feature subset with less iteration. However, the number of FFS method is considerably less than that of BFS method. More efficient FFS methods need to be developed. In this paper, two FFS methods based on the pruning of the classifier ensembles generated by single attribute are proposed for gene selection. The main contributions are as follows: (1) a new loss function, p-insensitive loss function, is proposed to overcome the disadvantage of the margin Euclidean distance loss function in the pruning of classifier ensembles; (2) two FFS methods based on the margin Euclidean distance loss function and the p-insensitive loss function, named as FFS-ACSA1 and FFS-ACSA2 respectively, are proposed; (3) the comparison experiments on four gene expression datasets show that FFS-ACSA2 obtains the best results among three FFS methods (i.e. signal-to-noise ratio (SNR), FFS-ACSA1 and FFS-ACSA2), and is competitive to the famous support vector machine-based recursive feature elimination (SVM-RFE), while FFS-ACSA1 is unstable.

Improving the computational efficiency of recursive cluster elimination for gene selection.

The gene expression data are usually provided with a large number of genes and a relatively small number of samples, which brings a lot of new challenges. Selecting those informative genes becomes the main issue in microarray data analysis. Recursive cluster elimination based on support vector machine (SVM-RCE) has shown the better classification accuracy on some microarray data sets than recursive feature elimination based on support vector machine (SVM-RFE). However, SVM-RCE is extremely time-consuming. In this paper, we propose an improved method of SVM-RCE called ISVM-RCE. ISVM-RCE first trains a SVM model with all clusters, then applies the infinite norm of weight coefficient vector in each cluster to score the cluster, finally eliminates the gene clusters with the lowest score. In addition, ISVM-RCE eliminates genes within the clusters instead of removing a cluster of genes when the number of clusters is small. We have tested ISVM-RCE on six gene expression data sets and compared their performances with SVM-RCE and linear-discriminant-analysis-based RFE (LDA-RFE). The experiment results on these data sets show that ISVM-RCE greatly reduces the time cost of SVM-RCE, meanwhile obtains comparable classification performance as SVM-RCE, while LDA-RFE is not stable.

Clinical analysis and follow-up study of chronic active Epstein-Barr virus infection in 53 pediatric cases.

BACKGROUND: Chronic active Epstein-Barr virus infection (CAEBV) has been previously reported to be sometimes associated with an aggressive clinical course. The characteristics of CAEBV in Mainland Chinese pediatric patients are largely unreported. The main aims of this survey were to recognize the clinical features of CAEBV in children and to explore its diagnostic criteria and risk factors. METHODS: A retrospective study was performed on 53 pediatric patients (36 boys and 17 girls) with CAEBV who were admitted to Beijing Children's Hospital between 2003 and 2007. All their medical records were reviewed and analyzed. For each patient, demographic, clinical, laboratory data and outcome were collected. Independent-samples t test was used for statistical analysis. RESULTS: The age at onset of CAEBV was from 2 months to 14.6 years (mean (5.3+/-3.3) years). At the time of onset, 43.4% patients had an infectious mononucleosis-like symptom. Most patients exhibited intermittent fever (92.5%, 49/53), hepatomegaly (81.1%, 43/53) and splenomegaly (77.4%, 41/53). Life-threatening complications including hemophagocytic syndrome (24.5%, 13/53), interstitial pneumonia (24.5%, 13/53), hepatic failure (15.1%, 8/53) and malignant lymphoma (11.3%, 6/53) were also observed. The serum EBV DNA level in 23 patients with CAEBV was in the range of 5.05 x 10(2)-4.60 x 10(6) copies/ml with a mean value of 10(3.7) copies/ml. Many patients with CAEBV generally had continuous symptoms during the observational period. Eleven out of 42 patients (26.2%) died 7 months to 3 years after onset. Deceased patients were more likely to have had lower platelet counts and albumin levels than the living patients (P<0.05 for all comparisons). CONCLUSIONS: The study reveals that CAEBV in Chinese pediatric patients has a severe clinical course and prognosis is poor. Thrombocytopenia and decreases in albumin might potentially be risk factors for a poor prognosis. EBV loads should be measured and tissue should be stained on hybridization probes for EBV-encoded small RNA (EBER) if a patient presents with the known symptoms of CAEBV.

Mutations in the perforin gene in children with hemophagocytic lymphohistiocytosis.

BACKGROUND: Recent studies have reported germline mutations in the perforin gene (PRF1) in some types of hemophagocytic lymphohistiocytosis (HLH). However, the prevalence of PRF1 mutations in HLH in Chinese pediatric patients has not been extensively studied. The aim of this study was to investigate the prevalence of mutations and sequence variations in the PRF1 gene in Chinese pediatric patients with HLH. METHODS: Polymerase chain reaction (PCR) was performed with five pairs of primers for the coding exons and the flanking intron sequences of PRF1. Sequencing of PCR products was subsequently applied in 30 pediatric patients with HLH and in 50 controls. RESULTS: Three heterozygous mutations in a coding region were found, which resulted in amino acid changes (C102F, S108N and T450M) in three patients. These mutations were not detected in control subjects. One patient had compound heterozygous mutations (S108N and T450M) in PRF1 as the background defect, and documented familial HLH type 2 (FHL2). One synonymous sequence variant (Q540Q) was observed in one patient but not in the controls. Two SNPs (A274A, H300H) in the coding region were detected in HLH patients and controls, but without differences in the heterozygosity rate between the two groups (P > 0.05 for all comparisons). CONCLUSIONS: We have identified three patients with three heterozygous missense mutations in PRF1; two of those three mutations (C102F and S108N) have so far been found only from Chinese patients. These findings are useful in evaluating the prevalence of PRF1 mutations in Chinese pediatric patients with HLH, and to correlate their genotype with phenotype. Some patients without familial history probably have primary HLH, which should be suspected even beyond the usual age range.