Yujie Zhong

Targeted inhibition of GATA-6 attenuates airway inflammation and remodeling by regulating caveolin-1 through TLR2/MyD88/NF-κB in murine model of asthma.

The purpose of this study was to evaluate the effects of GATA-6 on airway inflammation and remodeling and the underlying mechanisms in a murine model of chronic asthma. Female BALB/c mice were randomly divided into four groups: phosphate-buffered saline control (PBS), ovalbumin (OVA)-induced asthma group (OVA), OVA+ siNC and OVA+ siGATA-6. In this mice model, GATA-6 expression level was significantly elevated and the expression in Caveolin-1 (Cav-1) inversely correlated with the abundance of GATA-6 in OVA-induced asthma of mice. Silencing of GATA-6 gene expression upregulated Cav-1 expression. Additionally, downregulation of GATA-6 dramatically decreased OVA-challenged inflammation, infiltration, and mucus production. Moreover, silencing of GATA-6 resulted in decreased levels of immunoglobulin E (IgE) and inflammatory mediators and reduced inflammatory cell accumulation, as well as inhibiting the expression of important mediators including matrix metalloproteinase (MMP)-2 and MMP-9, TGF-β1, and a disintegrin and metalloproteinase 8 (ADAM8) and ADAM33, which is related to airway remodeling. Further analysis confirmed that silencing of GATA-6 attenuated OVA-induced airway inflammation and remodeling through the TLR2/MyD88 and NF-κB pathway. In conclusion, these findings indicated that the downregulation of GATA-6 effectively inhibited airway inflammation and reversed airway remodeling via Cav-1, at least in part through downregulation of TLR2/MyD88/NF-κB, which suggests that GATA-6 represents a promising therapeutic strategy for human allergic asthma.

Bioinformatics analysis of Rab GDP dissociation inhibitor beta and its expression in non-small cell lung cancer

BackgroundLung cancer has been considered as one of the most important causes of cancer-related mortality worldwide. To predict lung cancer, researchers identified several molecular markers. However, many underlying markers of lung cancer remain unclear. One of these markers is Rab GDP dissociation inhibitor beta (GDIβ), which is related to tumorigenicity, development and invasion. This study was designed to analyze the biological characteristics of Rab GDIβ and to detect the mRNA and protein expressions of Rab GDIβ in lung cancer cells; this study also aimed to investigate the functions of this protein in lung cancer.MethodUsing online software from the websites of NCBI, ProtParam and so on, we analyzed the biological characteristics of Rab GDIβ. RT-PCR was performed to detect gene expressions in A549 and 16HBE cell lines and immunohistochemistry (IHC) staining was conducted to detect Rab GDIβ protein expression in 57 cases of human lung cancer tissues and 19 cases of normal lung tissues. The association of protein expression with patient clinical and pathological characteristics was assessed in each dataset.ResultsBioinformatic analysis on Rab GDIβ: The mRNA of human Rab GDIβ contains two transcript variants; the common structural elements of the two proteins are mainly α-helix, random coil, β-turn and extended strand. Three and four transmembrane domains could be found in the entire polypeptide chain of protein variants 1 and 2, respectively; both transcript variants are hydrophilic and soluble proteins. The RT-PCR result: The mRNA expression of Rab GDIβ was down-regulation in A549 cells compared with that in 16HBE cells. The IHC result: The protein expression of Rab GDIβ in lung cancer cells was significantly lower than that in normal lung tissues (P <0.05) but was not correlated with patients’ age, gender, tumor size, pathological type, differentiation, lymph node metastasis, distant metastasis and TNM stage.ConclusionThe expression of Rab GDIβ was low in non-small cell lung cancer (NSCLC). Hence, Rab GDIβ may be a tumor suppressor and could function as an indicator of tumorigenesis in NSCLC; nevertheless, this result should be further studied.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_201

Quantitative proteomic analysis of mitochondrial proteins differentially expressed between small cell lung cancer cells and normal human bronchial epithelial cells: Mitochondrial proteins in lung cancer

Small cell lung cancer (SCLC) is highly aggressive and is associated with a dismal prognosis. However, there are no clinically recognized biomarkers for early diagnosis. In this study, we used quantitative proteomics to build differential mitochondrial protein profiles that may be used for early diagnosis and investigated the pathogenesis of lung cancer.

Bioinformatics analysis and expression study of fumarate hydratase in lung cancer

As its etiology and pathogenesis is obscure, illustrating the molecular mechanism of lung cancer has become a serious and urgent task. Studies have shown that fumarate hydratase (FH) is a tumor suppressor related to tumorigenesis, development, and invasion. Our aim was to analyze the biological information of FH, and detect the messenger ribonucleic acid (mRNA) and protein expression of FH in lung cancer cells to explore its role in tumorigenesis and in the development of lung cancer.

Long-term survival for 93 months of limited-stage small cell lung cancer: A case report and literature review

A 49‐year‐old man was diagnosed with small cell lung cancer in May 2005. Chemotherapy was started with 60 mg/day cisplatin iv drip (from days one to three), 2 mg topotecan (TP) hydrochloride iv drip (from days one to four), and traditional Chinese medicine (TCM) AiDi injection for anti‐tumor. After four cycles, he underwent conformal radiotherapy with 56Gy/28 fractions in October 2005. In April 2006, a mass on the right supraclavicular area was found. Therefore, he underwent another course of radiotherapy. The fields included the right supraclavicular area and the radiation dose was 50Gy/25 fractions. After completion of chemoradiotherapy, the patient achieved complete remission. Subsequently, the patient received prophylactic cranial irradiation (PCI). Until April of 2012, he had been followed up regularly. Since the SCLC diagnosis, he had received TCM for seven years. In April 2012, the patient complained of coughing again. Subsequently, the patient was given five cycles of an etoposide carboplatin regimen. A computed tomography (CT) scan was performed for review, which showed no obvious change. The patient underwent a second‐line chemotherapy irinotecan cisplatin three times. However, the symptoms and CT of this patient showed no significant improvement. We changed the chemotherapy regimen to TP (topotecan 1.2 mg iv drip, days one to five; carboplatin 100 mg iv drip, days one to five). After two TP regimens, the patient died in his sleep on 3 March 2013. In this case, the standardized sequential chemotherapy and radiotherapy treatment, PCI, TCM, and good compliance may have contributed to the patients longer survival.