Morphological characterization and molecular profiling of malignant pericardial effusion in patients with pulmonary adenocarcinoma

Context: Malignant pericardial effusions (MPCEs) is a common complication observed in advanced pulmonary adenocarcinoma. In such cases, investigating molecular alterations can have significant therapeutic implication in determining anticancer drugs. Aim: The objective was to evaluate the significance of cell block technique in the diagnosis of MPCE and further investigate the morphological and molecular profiles of MPCE in patients with pulmonary adenocarcinoma. Setting and Design: Cytopathological and molecular profiles of 19 MPCE cases in patients with pulmonary adenocarcinoma were retrospectively analyzed. The control group consisted of 14 malignant pleural effusion (MPE) cases in patients with pulmonary adenocarcinoma. Materials and Methods: Anaplastic lymphoma kinase (ALK) and tyrosine-protein kinase Met (C-MET) expression was evaluated by fluorescence in situ hybridization (FISH). Epithelial growth factor receptor (EGFR) and K-Ras (KRAS) mutations were detected by ARMS real-time polymerase chain reaction (RT-PCR). Statistical Analysis Used: Associations between MPCE and MPE were analyzed using Fisher's exact test. Results: MPCE was found to have micropapillary and solid pattern predominant with mucin secretion compared to acinar patterns, as seen in MPE. Seventeen MPCE cases (89.5%) and all MPE cases (100%) underwent molecular analysis. Mutations in EGFR and KRAS, ALK rearrangement, and C-MET amplification were observed in MPCE and MPE with statistical differences. Additionally, two MPCE cases demonstrated EGFR T790M mutation and multiple insertions at L858. Conclusions: MPCE shows micropapillary and solid cytological patterns predominant with mucin secretion. MPCE are suitable to analyze oncogenic mutations and to develop targeted therapy for patients with pulmonary adenocarcinoma. Further molecular investigations may reveal novel molecular alterations.

Excavation of attractor modules for nasopharyngeal carcinoma via integrating systemic module inference with attract method

The molecular mechanism of nasopharyngeal carcinoma (NPC) is poorly understood and effective therapeutic approaches are needed. This research aimed to excavate the attractor modules involved in the progression of NPC and provide further understanding of the underlying mechanism of NPC. Based on the gene expression data of NPC, two specific protein-protein interaction networks for NPC and control conditions were re-weighted using Pearson correlation coefficient. Then, a systematic tracking of candidate modules was conducted on the re-weighted networks via cliques algorithm, and a total of 19 and 38 modules were separately identified from NPC and control networks, respectively. Among them, 8 pairs of modules with similar gene composition were selected, and 2 attractor modules were identified via the attract method. Functional analysis indicated that these two attractor modules participate in one common bioprocess of cell division. Based on the strategy of integrating systemic module inference with the attract method, we successfully identified 2 attractor modules. These attractor modules might play important roles in the molecular pathogenesis of NPC via affecting the bioprocess of cell division in a conjunct way. Further research is needed to explore the correlations between cell division and NPC.

The accuracy of warfarin dosage based on VKORC1 and CYP2C9 phenotypes in a Chinese population.

Background: The aim of this study is to assess the accuracy of warfarin dosage based on VKORC1 and CYP2C9 genotype in Chinese population. Methods: Blood samples were taken from 37 patients. We compared the warfarin dosage obtained from genotype (according to www.warfarindosing.org) and treatment dosage with international normalized ratio (INR) value within 2.0-3.0. Results: The majority of Chinese people in our study are VKORC1 homozygous AA (89.2%), rarely VKORC1 heterozygous AG and we cannot find a patient with homozygous GG. For CYP2C9 genotype, most patients have the wildtype variants (CYP2C9*2 CC and CYP2C9*3 AA). The warfarin dosage for patients with VKORC1 AA and CYP2C9*3 AC is lower than for patients with other genotype variants. Conclusion: There is no significant difference between pharmacogenetic algorithm (www.warfarindosing.org) and our treatment dosage. Our conclusion is that the pharmacogenetic algorithm is accurate to predict the warfarin dose.