Xianghua Yi

The influence of dexamethasone on the proliferation and apoptosis of pulmonary inflammatory cells in bleomycin-induced pulmonary fibrosis in rats.

Objective:  The aim of this study was to investigate the inhibitory effect of dexamethasone on the state of proliferation/apoptosis of the pulmonary inflammatory cells in a rat pulmonary fibrosis model induced by bleomycin.

β-Catenin overexpression is associated with gefitinib resistance in non-small cell lung cancer cells

BACKGROUND Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) presents great challenges in the treatment of non-small cell lung cancer (NSCLC) patients, while the mechanisms are still not well understood. The β-catenin signaling pathway has been found to be associated with chemoresistance and can activate the EGFR and its downstream pathways. This study aimed to investigate the role of β-catenin in acquired resistance to EGFR-TKIs in NSCLC cell lines. METHODS The expression and transcriptional activity of β-catenin were measured in both the NSCLC cell line PC9 and its sub-line PC9/AB(2) which has acquired resistance to gefitinib. Knockdown and overexpression of β-catenin in the PC9/AB(2) and PC9 cells were performed. The cell survival rate and the activation of the EGFR and its downstream pathways were detected in the two cell lines after transfection. RESULTS Nuclear translocation of β-catenin was increased in the PC9/AB(2) cells and the baseline expression of members of the β-catenin signaling pathway was also higher in the PC9/AB(2) cells. Knocking down the expression of β-catenin increased the sensitivity of the PC9/AB(2) cells to gefitinib by blocking the activation of the EGFR downstream pathways, while β-catenin overexpression improved PC9 cells resistance to gefitinib by enhancing the activation of the EGFR and its downstream signaling. CONCLUSION β-catenin plays an important role in acquired resistance to EGFR-TKIs in NSCLC cell lines and may be a potential therapeutic target for NSCLC patients who have failed to respond to targeted therapy.

Clinical characteristics of amyloidosis with isolated respiratory system involvement: A review of 13 cases.

BACKGROUND: Isolated pulmonary amyloidosis is a very rare disease. METHODS: We retrospectively reviewed the records of patients with pathologically proven isolated pulmonary amyloidosis treated at our hospital from 1990 to 2011. RESULTS: There were 9 males and 4 females with a mean age of 54.7 years (range, 45–72 years) and the mean course of disease was 46.5 months (range, 5 months–15 years). The most common symptoms were cough (10/13), expectoration (8/13), hemoptysis (4/13), chest tightness (12/13), dyspnea (10/13), chest pain (3/13), fever (5/13), and body weight loss (2/13). Radiological findings included tracheal stenosis (2/13), bronchial stenosis with atelectasis (5/13), pulmonary nodules (3/13), lung consolidation (1/13), and lymph node enlargement with pleural effusion (2/13). Treatments included endotracheal stenting, endoscopic resection of tracheal and bronchial lesions, lung resection, and drug therapy with glucocorticoids, antineoplastic agents, or antibiotics. Four patients died of the disease within 1 year of diagnosis, 2 died of pneumonia at 3–4 years after original treatment, and the remaining patients are alive with follow-up ranging from 3 to 15 years. CONCLUSIONS: Isolated pulmonary amyloidosis is a rare disease with a relatively high mortality and its various manifestations make diagnosis challenging. Surgical resection of lesions and chemotherapy tend to be effective treatments.

Preventive effects of vitamin D treatment on bleomycin-induced pulmonary fibrosis.

Patients with pulmonary fibrosis often have low vitamin D levels, the effects of which are largely unknown. We here report that early vitamin D supplementation significantly reduced the severity of pulmonary fibrosis and inflammatory cell accumulationin in the bleomycin-induced pulmonary fibrosis mouse model on supplementary days 14, 21 and 28 (P < 0.001). Vitamin D supplementation also prevented some ultrastructural changes in response to bleomycin administration, including basement membrane thickening, interstitial fibrin deposition and microvilli flattening or disappearance on days 14, 21 and 28, and lamellar body swelling or vacuolation on days 21 and 28. The bleomycin group had rising hydroxyproline level on days 14, 21 and 28, whereas the vitamin D treatment group showed consistently lower hydroxyproline level but still higher than that of the control group (P < 0.001). Our immunohistochemistry and densitometry analyses showed less staining for α-smooth muscle actin, a myofibroblast marker, in the vitamin D group compared to the bleomycin group (P < 0.001). Thus, vitamin D treatment could prevent bleomycin-induced pulmonary fibrosis by delaying or suppressing ultrastructural changes, as well as attenuating hydroxyproline accumulation and inhibiting myofibroblastic proliferation. These data further our understanding of the roles of vitamin D in pulmonary fibrogenesis and in the treatment of pulmonary fibrosis.

TRAF6 promotes the invasion and metastasis and predicts a poor prognosis in gastric cancer

PURPOSE This study investigated the relationships of TRAF6 expression with clinical pathologic parameters and the prognosis of patients with gastric cancer. This study also explored the roles of TRAF6 in cell apoptosis and invasiveness, as well as underlying molecular mechanism of gastric cancer cell line in vitro. METHODS A total of 90 cases of tissue microarrays were immunohistochemically analyzed for TRAF6 expression. Cell proliferation was measured by MTT assay. Flow cytometry was used for analyzing cell apoptosis and cell invasion ability was detected by a Transwell invasion assay. Protein expression was assessed by Western blotting. RESULTS TRAF6 was expressed in 53 of 90 (58.9%) cases of gastric cancer. TRAF6 expression was significantly positively correlated with advanced N stage, pathological stage and a poor prognosis, but not an independent predictor of a poor prognosis in gastric cancer (p=0.083). The knockdown of TRAF6 increased cell apoptosis and reduced invasive ability of BGC-823 cell. Moreover, TRAF6 down-regulation decreased protein levels of phosphor-Akt, Bcl-2 and MMP9 and up-regulation of Bax in BGC-823 cell. Inversely, overexpression of TRAF6 in SGC-7901 cells increased protein levels of phosphor-Akt, Bcl-2 and MMP9 and down-regulation of Bax. CONCLUSIONS The expression of TRAF6 was positively correlated with an advanced N stage and acted as a predictor of a poor prognosis in patients with gastric cancer. Moreover, TRAF6 regulating cell apoptosis and invasive ability of gastric cancer cells might be associated with Akt activation and alterations of protein expression of Bcl2, Bax and MMP9.

The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphoma

Abstract Latest study showed that a novel translocation between programmed cell death ligand 1 (PD-L1) (cluster of differentiation 274) and TP63 (tumor protein 63) can be found in diffuse large B-cell lymphoma (DLBCL), resulting in their conjunct overexpression in tumor cells at RNA level. However, the expressed pattern of these 2 genes at protein level in DLBCL remains largely unknown, and the clinical relevance of PD-L1 and TP63 expression in DLBCL are also unclear. Tumor tissues from 76 Chinese DLBCL patients were immunostained for programmed cell death 1 (PD-1), PD-L1, and TP63 using the EnVision system. Clinical relevance of PD-1, PD-L1, and TP63 in 74 DLBCL were analyzed by chi-square test, the Kaplan–Meier curves with log rank test, and Coxs proportional hazards regression model. PD-1 was mainly expressed in tumor-infiltrating lymphocytes (TILs) of 39.5% patients. PD-L1 was expressed in tumor cells of 26.3% patients, and TP63 was immunostained in nucleoli of tumor cells of 31.6% cases. PD-1 expression was significantly associated with the patients’ gender and B symptoms (P = 0.032, P = 0.026). DLBCL with PD-L1 or TP63 expression in tumor cells showed low International Prognostic Index (IPI) score (P = 0.007, P = 0.009). PD-1+ TILs was related to prolonged overall survival rate (OS) of DLBCL patients (P = 0.02), whereas PD-L1 expression was associated with worse clinical outcome of patients (P = 0.049). Immunoreactivity of TP63 was not correlated with patients’ survival time. Besides, PD-1 expression, patients’ age, Ann Arbor stage, and IPI score were significant prognostic markers for OS, but PD-L1 and TP63 had no prognostic significance. PD-1, PD-L1, and TP63 are frequently expressed in DLBCL. PD-1/PD-L1/TP63 blockade may be a potential therapeutic strategy for some patients.

Protein-protein interaction analysis of distinct molecular pathways in two subtypes of colorectal carcinoma

The aim of this study was to identify the molecular events that distinguish serrated colorectal carcinoma (SCRC) from conventional colorectal carcinoma (CCRC) through differential gene expression, pathway and protein-protein interaction (PPI) network analysis. The GSE4045 and GSE8671 microarray datasets were downloaded from the Gene Expression Omnibus database. We identified the genes that are differentially expressed between SCRC and normal colon tissues, CCRC and healthy tissues, and between SCRC and CCRC using Student’s t-tests and Benjamini-Hochberg (BH) multiple testing corrections. The differentially expressed genes (DEGs) were then mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and their enrichment for specific pathways was investigated using the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool with a significance threshold of 0.1. Analysis of the potential interactions between the protein products of 220 DEGs (between CCRC and SCRC) was performed by constructing a PPI network using data from the high performance RDF database (P<0.1). The interaction between pathways was also analyzed in CCRC based on the PPI network. Our study identified thousands of genes differentially expressed in SCRC and CCRC compared to healthy tissues. The DEGs in SCRC and CCRC were enriched in cell cycle, DNA replication, and base excision repair pathways. The proteasome pathway was significantly enriched in SCRC but not in CCRC after BH adjustment. The PPI network showed that tumour necrosis factor receptor-associated factor 6 (TRAF6) and atrophin 1 (ATN1) were the most central genes in the network, with respective degrees of node predicted at 90 and 88. In conclusion, the preoteasome pathway was shown to be specifically enriched in SCRC. Furthermore, TRAF6 and ATN1 may be promising biomarkers for the distinction between serrated and conventional CRC.

Transmission electron microscopy of sputum deposition in the diagnosis of pulmonary alveolar proteinosis.

Objective: To clarify the diagnostic value of sputum in pulmonary alveolar proteinosis (PAP) through transmission electron microscopy (TEM) of sputum deposition (SD). Methods: Eleven SD samples and 9 bronchoalveolar lavage (BAL) sediments from a PAP group including 11 patients were observed by TEM and compared with sputum direct smear, BAL cytology, and lung biopsy histopathology. Eleven healthy adults were chosen as controls. Results: The 11 sputum smears from the PAP group showed no diagnostic component, but TEM of SD revealed 7 of 11 samples had many myelin-like lamellar bodies with degeneration in the cytoplasm of macrophages, alveolar epithelial cells, and extracellular spaces, which suggested PAP. Especially, 2 patients on whom lung biopsy could not be performed and who failed to be diagnosed by BAL fluid were finally diagnosed by TEM of SD. TEM of BAL sediments showed 7 of 9 cases had diagnostic myelin-like lamellar bodies. No statistical significance was found between BAL fluid and SD by TEM. The control group didn’t show diagnostic components by cytology or TEM of SD. Conclusion: TEM of SD is an important noninvasive diagnostic method especially for patients against lung biopsy and BAL.

Clinicopathologic and Ultrastructural Study of Non-HIV-related Primary Pulmonary Cryptococcosis in China: Report of 43 Cases

Objective: To clarify the clinicopathologic and ultrastructural features of primary pulmonary cryptococcosis (PC). Methods: 43 cases of PC were observed by light microscopy and histochemical staining, including mucicarmine (MC), Alcian blue (AB), periodic acid–Schiff (PAS), and Grocott methenamine–silver (GMS). Transmission electron microscopy (TEM) was performed on 11 fresh and 8 formalin-fixed specimens. Results: The detective rate of Cryptococcus neoformans (CN) by MC, AB, PAS, GMS staining, and TEM was 61.3% (19/31), 62.2% (23/37), 85.7% (30/35), 79.1% (34/43), and 89.5% (17/19), respectively. All CN detected by TEM had a capsule. Most of them possessed simple structure with undeveloped cellular organelles. Conclusion: Electron microscopy has a high rate of detecting CN. A combination of histochemical staining and electron microscopy can make an accurate diagnosis of PC.

Analysis of Microarray-Identified Genes and MicroRNAs Associated with Idiopathic Pulmonary Fibrosis

The aim of this study was to identify potential microRNAs and genes associated with idiopathic pulmonary fibrosis (IPF) through web-available microarrays. The microRNA microarray dataset GSE32538 and the mRNA datasets GSE32537, GSE53845, and GSE10667 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DE-miRNAs)/genes (DEGs) were screened with GEO2R, and their associations with IPF were analyzed by comprehensive bioinformatic analyses. A total of 45 DE-microRNAs were identified between IPF and control tissues, whereas 67 common DEGs were determined to exhibit the same expression trends in all three microarrays. Furthermore, functional analysis indicated that microRNAs in cancer and ECM-receptor interaction were the most significant pathways and were enriched by the 45 DE-miRNAs and 67 common DEGs. Finally, we predicted potential microRNA-target interactions between 17 DE-miRNAs and 17 DEGs by using at least three online programs. A microRNA-mediated regulatory network among the DE-miRNAs and DEGs was constructed that might shed new light on potential biomarkers for the prediction of IPF progression.