APOE genotype is a risk factor for Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). The risk and severity of CAA increase with possession of APOE ɛ4, whereas APOE ɛ2 increases the risk of vessel rupture. Uptake of Aβ by cerebrovascular smooth muscle cells (CVSMCs) is mediated by low-density lipoprotein ...

ABSTRACT: BACKGROUND: BRCA1 (B), ERCC1 (E), RRM1 (R) and TYMS (T) mRNA expression has been extensively studied with respect to NSCLC patient outcome upon various chemotherapy agents. However, these markers have not been introduced into clinical practice yet. One of the reasons seems to be lack of a standard approach ...

Asthma exacerbations can be caused by a number of factors, including the fungal allergen Alternaria, which is specifically associated with severe and near-fatal attacks. The mechanisms that trigger lung responses are unclear and might vary between allergens. A comparison between Alternaria, Aspergillus, Candida, and house dust mite, all allergens in ...

Goblet cell hyperplasia (GCH) and mucous hypersecretion are common pathological features of chronic pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and cystic fibrosis. Despite numerous studies, the molecular basis for this condition remains elusive. Gab2 is a member of the Dos/Gab subfamily scaffolding molecules and plays ...

To explore the relationship between the immunohistochemical expression of E-cadherin and the relevant clinicopathologic features in various types of melanocytic nevi and cutaneous malignant melanoma (CMM). Using standard immunohistochemical techniques, we examined 30 CMMs, 30 melanocytic nevi and 10 sex- and age-matched volunteers for the expression of E-cadherin. A total ...

Environmental exposure to benzene occurs through cigarette smoke, unleaded gasoline and certain types of plastic. Benzene is converted to hematotoxic metabolites by the hepatic phase-I enzyme CYP2E1, and these metabolites are detoxified by the phase-II enzyme NQO1. The genes encoding these enzymes are highly polymorphic and studies of these polymorphisms ...

FoxP1 has been reported to be expressed in several types of human malignant tumors, and has been associated with metastasis and patient prognosis. Quantitative real-time polymerase chain reaction (PCR) and immunohistochemical analysis with tissue microarray were used to characterize the expression of FoxP1 in non-small cell lung cancer (NSCLC). It ...

The metastasis-associated lung adenocarcinoma transcript 1, MALAT1, is a long non-coding RNA (lncRNA) that has been discovered as a marker for lung cancer metastasis. It is highly abundant, its expression is strongly regulated in many tumor entities including lung adenocarcinoma and hepatocellular carcinoma as well as physiological processes, and it ...

Metastatic cancer is extremely difficult to treat, and the presence of metastases greatly reduces a cancer patient's likelihood of long-term survival. The ZEB1 transcriptional repressor promotes metastasis through downregulation of microRNAs (miRs) that are strong inducers of epithelial differentiation and inhibitors of stem cell factors. Given that each miR can ...

The radiation doses used to treat unresectable lung cancer are often limited by the proximity of normal tissues. Overexpression of c-Met, a receptor tyrosine kinase, occurs in about half of non-small-cell lung cancers (NSCLCs) and has been associated with resistance to radiation therapy and poor patient survival. We hypothesized that ...

There are no established reports about the expression of the Piwil gene, a subfamily of the Piwi gene involved in RNA silencing and self-renewal, in colorectal carcinomas. It is known that the degree of PIWIL2 expression is higher in colorectal carcinomas. But its clinicopathologic significance remains undetermined. This study reassessed ...

BACKGROUND: The purpose of the present study was to clarify the prognostic significance of human leukocyte antigen (HLA) class I expression in patients with non-small-cell lung cancer who underwent complete surgical resection. PATIENTS AND METHODS: The expression of HLA class I molecules was evaluated in 403 resected NSCLC specimens using ...

Dermal papilla cells (DPCs) have the potential to induce differentiation of epithelial stem cells into hair, and Wnt signaling is deeply involved in the initiation process. The functional limitation of expanded adult DPCs has been a difficult challenge for cell-based hair regrowth therapy. We previously reported that 1α,25-dihydroxyvitamin D(3) (VD(3)) ...

NR0B1, an orphan nuclear receptor, is expressed in side population cells and its knockdown reduces tumorigenic and anti-apoptotic potential in lung adenocarcinoma. Peroxisome proliferator-activated receptor γ (PPARγ) is another member of the nuclear receptor family which induces apoptosis in lung cancer. The interaction of NR0B1 with PPARγ was examined. The ...

While Kras/mitogen-activated protein kinase (MAPK) and canonical Wnt/β-catenin are critical for lung morphogenesis, mechanisms integrating these important signaling pathways during lung development are unknown. Herein, we demonstrate that the Foxm1 transcription factor is a key downstream target of activated Kras(G12D). Deletion of Foxm1 from respiratory epithelial cells during lung formation ...

Particulate pollution is suspected to contribute to obstructive lung diseases characterized by chronic inflammation, mucus hypersecretion and bronchial remodeling. Our aim was to study the effect of real-world particulate matter (PM) on the expression of a mucin, MUC5AC, focusing on the role of the epidermal growth factor receptor (EGFR) pathway. ...

Accumulating evidence indicates that mitogen-activated protein 4 kinase 4 (MAP4K4) is frequently overexpressed in many types of human cancers, and plays important roles in transformation, invasiveness, adhesion, and cell migration. The aim of the present study was to explore the expression and prognostic significance of MAP4K4 in lung adenocarcinoma. The ...

We previously identified cathepsin D as a possible marker for lung adenocarcinoma (AD). The purpose of the present study is to evaluate the correlation between cathepsin D expression and clinicopathological findings or prognosis. We conducted immunohistochemistry (IHC) to assess 150 AD tissues. For these 150 tumors, TTF-1 expression, EGFR and ...

Pulmonary carcinoids, distinct in typical and atypical, represent 2-5% of all primary lung tumors. The aim of this study was to investigate the molecular alterations correlated with the development of this form of neoplasms. A collection of 38 paraffin-embedded apparently sporadic carcinoids was investigated, through a combined study, for protein ...

Embryonic development of the respiratory system is regulated by a series of mesenchymal-epithelial interactions that are only partially understood. Mesenchymal FGF and Wnt2/Wnt2b signaling are implicated in specification of mammalian pulmonary progenitors from the ventral foregut endoderm, but their epistatic relationship and downstream targets are largely unknown. In addition, how ...

Pax genes encode highly conserved transcription factors vital for metazoan development. Pax transcripts, particularly those in Group II (Pax2/5/8), are extensively alternatively spliced. This study compares the transcriptional activation capacity and developmental stage-specific expression of major isoforms of Group II Pax proteins in amphioxus (Branchiostoma floridae) and in Xenopus laevis. ...

ABSTRACT: BACKGROUND: The BH3-only members of the Bcl-2 protein family have been proposed to play a key role in the control of apoptosis and in the initiation of the apoptotic pathways. In this study, we evaluated the expression of Bim, Noxa, and Puma in non-small cell lung cancer (NSCLC). METHODS: ...

Human lung fibroblasts are a potential source of endothelin-1 (ET-1), a pro-fibrotic mediator. The present study explored possible muscarinic and β-adrenergic modulations of ET-1 expression in human lung fibroblasts. MRC-5 human lung fibroblasts were cultured. Expression of prepro-endothelin-1 (ppET-1) mRNA was determined by quantitative real time PCR. [(3)H]-Proline incorporation was ...

Lung adenocarcinoma is the most frequently histologic subtype and the most histologically heterogeneous form of lung cancer. De-regulation of Wnt/β-catenin signaling pathway is implicated in lung carcinogenesis. SOX7, as a member of high mobility group (HMG) transcription factor family, plays a role in the modulation of the Wnt/β-catenin signaling pathway. ...

Annexin-A1 (AnxA1) is a glucocorticoid-induced protein with multiple actions in the regulation of inflammatory cell activation. The contribution of AnxA1 to human cell biology is not well understood. We investigated the contribution of AnxA1 and its receptor, formyl-peptide receptor 2 (FPR2), to the regulation of inflammatory responses in human normal ...

Adenosine triphosphate regulates NADPH oxidase activity leading to hydrogen peroxide production and COX-2/PGE(2) expression in A549 cells. Am J Physiol Lung Cell Mol Physiol ___:L___-L___, 2012. Non-small cell lung carcinoma (NSCLC) accounts for most of all lung cancers, which is the leading cause of mortality in human being. High level ...

In bronchopulmonary dysplasia (BPD), alveolar septa are thickened with collagen and α-smooth muscle actin-, transforming growth factor (TGF)-β-positive myofibroblasts. We examined the biochemical mechanisms underlying myofibroblastic differentiation, focusing on the role of glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway. In the cytoplasm, β-catenin is phosphorylated on the NH(2) terminus by constitutively ...

Disturbance of hemostatic balance associated with increased tissue factor (TF) expression and activity occurs in the lungs of idiopathic pulmonary fibrosis (IPF) patients. However, the molecular mechanisms responsible for regulation of TF expression under pro-fibrotic conditions have not yet been assessed. We found that transforming growth factor-β1 (TGF-β1) markedly enhanced ...

The expression of multidrug-resistant protein-3 (MRP3), a membrane-bound transporter, has been linked to drug resistance in non-small cell lung cancers (NSCLCs). Recently, we reported that NRF2 gene (NFE2L2) mutations are correlated with poor prognosis for lung squamous cell carcinomas. We hypothesized that tumor MRP3 expression may be correlated with the ...

New pharmacologic targets are needed for lung cancer. One candidate pathway to target is composed of the E1-like ubiquitin-activating enzyme (UBE1L) that associates with interferon-stimulated gene 15 (ISG15), which complexes with and destabilizes cyclin D1. Ubiquitin protease 43 (UBP43/USP18) removes ISG15 from conjugated proteins. This study reports that gain of ...

The thyroid transcription factor 1 gene (TTF-1 or NKX2-1) is essential to lung development; however, it is also a critical factor in lung cancer. TTF-1 is amplified in lung cancers, suggesting that it is a gain-of-function lung oncogene. Conversely, TTF-1 counters epithelial to mesenchymal transition in cell-based studies and inhibits ...

Asthma is a disease characterized by chronic airway inflammation, and Th2 cells play a critical role in initiating and sustaining asthmatic inflammation. It has been shown that CD44 expressed on CD4(+) T cells plays a critical role in the accumulation of antigen-specific Th2 cells in the development of airway hyperresponsiveness ...

We were interested in determining how the tumor suppressor gene RBM5 is regulated in lung cancers. Previous studies suggested that the gene expression is related to histological subtype and smoking exposure, since in small cell lung cancers the RBM5 gene is deleted whereas in non-small cell lung carcinomas (NSCLC) RBM5 ...

Cisplatin is a classic chemotherapy agent used for treating human non-small cell lung cancer (NSCLC). However, cisplatin resistance is a challenge against successful clinical use. Glutathione S-transferase P1 (GSTP1) has been reported to contribute to cisplatin resistance in many studies. MicroRNAs (miRNAs) are short non-coding RNAs that are 21-25 nucleotides ...

MicroRNAs (miRNA) are important noncoding regulatory molecules that bind target messenger RNA (mRNA), primarily affecting their translation into protein. Because miRNAs can simultaneously target hundreds of mRNAs, subtle changes in their expression can elicit important cellular effects. Little is known about the role of miRNAs in pulmonary responses to inhaled ...

PURPOSE: Overexpression of DNA 5'-cytosine-methyltransferase 3A (DNMT3A), which silences genes including tumor suppressor genes (TSGs), is involved in many cancers. Therefore, we examined whether the transcriptional deregulation of RB/MDM2 pathway was responsible for DNMT3A overexpression and analyzed the therapeutic potential of MDM2 antagonist for reversing aberrant DNA methylation status in ...

ABSTRACT: BACKGROUND: The mechanisms underlying the association between smoking and mucus overproduction remain unknown. Because of its involvement in other airway diseases, such as asthma, we hypothesized that Ca2+-activated Cl- channel 1 (CLCA1) was associated with overproduction of mucus in the airways of smokers and COPD patients. METHODS: Using real-time ...

Lung adenocarcinoma, the most common type of human non-small cell lung cancer (NSCLC), frequently overexpresses epidermal growth factor receptor (EGFR). However, the mechanisms underlying EGFR overexpression are not completely understood. Recent studies have identified that decreased expression of TIP30 (30kDa HIV-1 Tat interacting protein) is associated with the metastasis of ...

The regulation of mesenchymal cell growth by signaling molecules plays an important role in maintaining tissue functions. Aberrant mesenchymal cell proliferation caused by disruption of this regulatory process leads to pathogenetic events such as fibrosis. In the current study we have identified a novel nuclear factor, Phf14, which controls the ...

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology. A conspicuous feature is the formation and persistence of fibroblastic/myofibroblastic foci throughout the lung parenchyma. Mechanisms remain unknown, but data indicate that fibroblasts acquire an anti-apoptotic phenotype. We hypothesized that transcriptional silencing of pro-apoptotic genes may be implicated, ...

Aims: Oxidants have been implicated in the pathophysiology of idiopathic pulmonary fibrosis (IPF), especially in myofibroblastic differentiation. We aimed to test the hypothesis that nuclear factor erythroid 2 related factor 2 (Nrf2), the main regulator of endogenous antioxidant enzymes, is involved in fibrogenesis via myofibroblastic differentiation. Methods: Fibroblasts were cultured ...

Cigarette smoke (CS) exposure is associated with increased mucus production and chronic obstructive pulmonary disease (COPD). MUC5AC is the major inducible mucus gene in the airway. The purpose of this investigation was to elucidate the mechanisms of CS-induced activation of MUC5AC gene transcription. We observed that the region -3724/-3224 of ...

ABSTRACT: BACKGROUND: Pirfenidone is a novel anti-fibrotic and anti-inflammatory agent that inhibits the progression of fibrosis in animal models and in patients with idiopathic pulmonary fibrosis (IPF). We previously showed that pirfenidone inhibits the over-expression of collagen type I and of heat shock protein (HSP) 47, a collagen-specific molecular chaperone, ...

The purpose of this study was to investigate the expression of Raf kinase inhibitor protein (RKIP) and epithelial cadherin (E-cadherin) in lung squamous cell carcinoma tissue and its correlation with the clinical pathology of lung squamous cell carcinoma. RKIP and E-cadherin mRNA (by RT-PCR) and protein (by western blotting) levels ...

Our previous data suggested that the human basic helix-loop-helix transcription factor achaete- scute homolog-1 (hASH1) may stimulate both proliferation and migration in the lung. In the CNS cyclin-dependent kinase 5 (Cdk5) as well as its activator p35 are important for neuronal migration that is regulated by basic helix-loop-helix transcription factors. ...

BACKGROUND: Subcellular localization of apurinic/apyrimidinic endonuclease-1/redox factor-1 (Ape1) has been demonstrated to promote lung tumor malignancy via NF-κB activation. We hypothesized that increased cytoplasmic Ape1 expression might cause NF-κB activation by p53 aberration, and result in poor outcome in non-small cell lung cancer (NSCLC). METHODS: Herein, knockdown of E6 or ...

Bronchial mucins from severely infected patients suffering from lung diseases such as chronic bronchitis or cystic fibrosis exhibit increased amounts of sialyl-Lewis(x) (NeuAcΑ2-3GalΒ1-4[FucΑ1-3]GlcNAc-R, sLe(x)) glycan structures. In cystic fibrosis, sLe(x) and its sulfated form 6-sulfo-sialyl-Lewis(x) (NeuAcΑ2-3GalΒ1-4[FucΑ1-3](HO(3)S-6)GlcNAc-R, 6-sulfo-sLe(x)) serve as receptors for Pseudomonas aeruginosa and are involved in the chronicity of ...

Paraquat (1,1'-dimethyl-4,4'-bipyridinium chloride; PQ) is widely and commonly used as a herbicides in the world. PQ has been reported to be a major hazard because it causes lung injury. However, the molecular mechanisms underlying PQ-induced lung toxicity still need to be elucidated. Here, we found that PQ significantly decreases cell ...

Complexes between mRNA and GL67:DOPE:DMPE-PEG5000 (GL67) liposomes were formulated and characterized. Subsequently, the in vitro and in vivo expression characteristics of mRNA/GL67 complexes and pDNA/GL67 complexes, each produced at their optimal ratio, were compared in respiratory cells. Transfection of A549 cells with mRNA/GL67 complexes resulted in a much faster expression ...

Pulmonary arterial endothelial cells (PAECs) express the enzymes needed for generation of l-arginine from intracellular l-citrulline but do not express the enzymes needed for de novo l-citrulline synthesis. Hence, l-citrulline levels in PAECs are dependent on l-citrulline transport. Once generated, l-arginine can be converted to l-citrulline and nitric oxide (NO) ...