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Objective: To systematically review the effect and safety of irinotecan plus cisplatin (IP) compared with etoposide plus cisplatin (EP) in patients with previously untreated extensive-stage small cell lung cancer (E-SCLC).Materials and Methods: Databases including PubMed, The Cochrane Library, EMBASE, China National Knowledge Infrastructure, VIP, and WanFang Data were searched for the randomized controlled trials (RCTs) about IP compared with EP in patients with previously untreated E-SCLC from the establishment to June 2016. Two reviewers independently screened literature, extracted data and assessed the methodological quality of included studies. Then meta-analysis was performed using RevMan 5.3 software (Cochrane Collaboration, Oxford, UK).Results: A total of 12 RCTs involving 2030 patients were finally included. Meta-analysis showed that compared with EP regimen, IP regimen significantly improved the 1- and 2-year survival rates of the patients with previously untreated E-SCLC (risk ratio [RR] = 1.16, 95% confidence interval [CI] [1.03-1.31], P = 0.02; RR = 1.79, 95% CI [1.22-2.61], P = 0.003, respectively). However, there was no significant difference between IP regimen and EP regimen in the objective response rate (ORR) (RR = 1.07, 95% CI [0.99-1.15], P = 0.10) and disease control rate (DCR) (RR = 1.03, 95% CI [0.96-1.10], P = 0.38). The incidence of Grade 3/4 leukopenia, neutropenia, anemia, and thrombocytopenia of IP regimen was sigificantly lower than EP regimen (all P < 0.05), the incidence of Grade 3/4 nausea/vomiting and diarrhea of IP regimen was sigificantly higher than EP regimen (all P < 0.05).Conclusion: IP regimen significantly improves the 1- and 2-year survival rates, but not significantly improves the ORR and DCR, compared with EP regimen in patients with previously untreated E-SCLC. IP regimen has less Grade 3 or 4 hematological adverse events. IP regimen is an alternative of EP regimen in patients with previously untreated E-SCLC. [ABSTRACT FROM AUTHOR]

Various eukaryotic translation initiation factors (eIFs) have been implicated in carcinoma development. Eukaryotic translation initiation factor 3 subunit D (eIF3D) has recently been shown to regulate the growth of several types of human cancer cells. However, the function of eIF3D in acute myeloid leukemia (AML) remains unclear. In this study, we investigated the expression of eIF3D in three AML cell lines and a lymphoblast cell line, and found that eIF3D was expressed in all four leukemia cell lines. To explore the role of eIF3D in AML cell proliferation, lentivirus-mediated RNA interference was applied to knock down the expression of eIF3D in U937 cells. The expression of eIF3D was significantly downregulated in U937 cells after eIF3D knockdown, as confirmed by quantitative real-time PCR (qRT-PCR) and Western blot analysis. Knockdown of eIF3D significantly inhibited proliferation of U937 cells. Furthermore, flow cytometry analysis revealed that eIF3D silencing induced cell cycle arrest at the G2/M phase, ultimately leading to apoptosis. Our results indicate that eIF3D plays a key role in the proliferation of AML cells, and suggest that eIF3D silencing might be a potential therapeutic strategy for leukemia. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the effect and molecular mechanisms of Haishengsu (HSS), a protein extract from a shellfish Tegillarca granosaL., on a drug resistant leukemia cell line. Cultured K562/Adriamycin (ADM) cells were treated with HSS at 10, 20 and 40 μg/mL, respectively. The apoptosis and expression of p-glycoprotein was evaluated by flow cytometry. Expressions of caspase-3 and Bcl-2 were also evaluated. There was a significant dose-dependent increase in the apoptosis in the HSS treated K562/ADM cells (P < 0.05 and 0.01, respectively). The p-glycoprotein expression in the 40 μg/mL HSS group (14.8%) was lower than in the control (16.9%, P < 0.05) and the 10 μg/mL HSS group (7.3%, P < 0.05), but it was similar to the HSS 20 μg/mL group (10.7%, P > 0.05). The expressions of apoptosis-stimulating protein caspase-3 protein were increased, whereas the expressions of apoptosis-suppressing Bcl-2 were decreased in the HSS groups, as compared with the levels in the control group (P < 0.05). We conclude that HSS induces apoptosis of the Adriamycin-resistant K562/ADM cells. The enhanced expressions in caspase-3 and the reduced expressions in Bcl-2 protein may have contributed to the apoptosis-stimulating effect of HSS. The inhibition of p-glycoprotein suggests that HSS may diminish the resistance to Adriamycin and potentially enhance the therapeutic effects. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by expansion of the fibroblast and myofibroblast population and extracellular matrix deposition. Although the pathogenic mechanisms of IPF remain to be fully elucidated, there is emerging evidence that fibroblasts and myofibroblasts may be derived partially from alveolar epithelial cells by epithelial‑mesenchymal transition (EMT). In the present study, A549 cells were treated with different concentrations of Wnt1 and the results indicated that the mRNA and protein expression levels of vimentin, α‑smooth muscle actin (α‑SMA) and collagen Ⅰ gradully increased and those of E‑cadherin gradully decreased in a concentration‑dependent manner. Furthermore, the A549 cells were transfected with β‑catenin plasmid cells, revealing phenotypic changes in the cells from a pebble to a fusiform shape. The mRNA and protein expression levels of of vimentin, α‑SMA and collagen Ⅰ increased significantly, whereas those of E‑cadherin decreased significantly. The present study examined the roles of alveolar epithelial cell injury and profibrogenic cytokine release in EMT and their association with the Wnt/β‑catenin signaling pathway in a mouse model of bleomycin‑induced pulmonary fibrosis. Bronchoalveolar fluid was obtained 7 days after treatment with bleomycin and the A549 cells were incubated for 48 h. An increase in the expression levels of the mesenchymal markers, α‑SMA, vimentin and collagen Ⅰ, and a concomitant decrease in the expression of the epithelial marker, E‑cadherin were observed. This corresponded with an increased expression of β‑catenin. When the A549 cells were infected with a lentivirus expressing β‑catenin shRNA, no significant increase was observed in the expression of the mesenchymal cell markers and the expression of E‑cadherin did not decrease. These findings demonstrated that activation of the Wnt signaling pathway was capable of inducing an EMT program in the lung epithelial cells through β‑catenin and that injured alveolar epithelium activated the Wnt/β‑catenin signaling pathway, thereby inducing the expansion of the fibroblast/myofibroblast population through EMT. These results suggested that β‑catenin was involved in the formation of lung fibrosis and may provide a theoretical basis for the treatment of IPF.

Objective: To study the in vitro effect and mechanism of Napsin A gene transfection into type II alveolar epithelial cells on pulmonary fibrosis., Methods: A recombinant lentiviral plasmid PLJM1-Napsin A was constructed and transfected into human type II alveolar epithelial cell line A549. The model of pulmonary fibrosis was established by the in vitro stimulation of A549 cells by transforming growth factor beta-1 (TGF-β1). The morphological changes were observed continuously under inverted microscopy. The proliferation of transgenic and non-transgenic cells was detected by MTT. To observe the degree of epithelial-mesenchymal transition (EMT) by TGF-β1 intervening A549 cells, the expressions of E-cadherin and fibronectin were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Lastly the protein expression of focal adhesion kinase (FAK) was detected by Western blot to investigate the mechanism., Results: The result of sequencing the recombinant lentiviral plasmid PLJM1-Napsin A was the same as the design sequence. Napsin A mRNA and protein were expressed in transgenic A549 cells (P<0.01). The model of pulmonary fibrosis was established successfully based on the morphology of transformed interstitial cell. As compared with the control group, the proliferation rate of transgenic cells decreased significantly (P<0.05). The mRNA and protein expression of E-cadherin significantly decreased in the model of pulmonary fibrosis (P<0.01), while the expression of fibronectin markedly increased (P<0.01). But the change rate of transgenic cells decreased (P<0.01, P<0.05). The expression of FAK was significantly elevated after the stimulation of TGF-β1 (P<0.01). But the upward trend of the transgenic cells was smaller as compared with the control group (P<0.01)., Conclusion: Pulmonary fibrosis may be suppressed by the transfection of Napsin A gene into type II alveolar epithelial cells. And the mechanism may be through the inhibition of integrin signal transduction.