Lung Cancer and Environmental Chemical Exposure: A Review of Our Current State of Knowledge With Reference to the Role of Hormones and Hormone Receptors as an Increased Risk Factor for Developing Lung Cancer in Man

2010 ◽  
Vol 38 (6) ◽  
pp. 849-855 ◽  
Author(s):  
Alexsandra Fucic ◽  
Marija Gamulin ◽  
Zeljko Ferencic ◽  
Dinko Stancic Rokotov ◽  
Jelena Katic ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Hormone Receptors ◽  
Current Knowledge ◽  
Biological Effects ◽  
Chemical Exposure ◽  
Living Environment ◽  
Human Lung Cancer ◽  
Cancer Etiology ◽  
Environmental Chemical ◽  
Increased Risk

Lung cancer is a dominant cause of cancer mortality. The etiology of lung cancer is mainly related to cigarette smoking, airborne genotoxic carcinogens, and arsenic, but its sex-specific incidence suggests that other mechanisms, such as hormones, may also be involved in the process of carcinogenesis. A number of agents commonly present in the living environment can have dual biological effects: not only are they genotoxic / carcinogenic, but they are also hormonally active as xenoestrogens. This dualism may explain sex-specific differences reported in both types and incidence of lung cancer. In a novel approach to investigate the complexity of lung cancer, etiology, including systems biology, will be used as a tool for a simultaneous interpretation of measurable environmental and biological parameters. Using this approach, the etiology of human lung cancer can be more thoroughly investigated using the available data from oncology and environmental health. The information gained could be applied in the introduction of preventive measures, in personalized medicine, and in more relevant legislation, which should be adjusted to reflect the current knowledge on the complex environmental interactions underlying this life-threatening disease.

scholarly journals MicroRNA-7–regulated TLR9 signaling–enhanced growth and metastatic potential of human lung cancer cells by altering the phosphoinositide-3-kinase, regulatory subunit 3/Akt pathway

2013 ◽  
Vol 24 (1) ◽  
pp. 42-55 ◽  
Author(s):  
Lin Xu ◽  
Zhenke Wen ◽  
Ya Zhou ◽  
Zhongmin Liu ◽  
Qinchuan Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Human Lung ◽  
Biological Effects ◽  
Tumor Biology ◽  
Metastatic Potential ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Human Lung Cancer Cells ◽  
Tlr9 Signaling

Recent evidence shows that microRNAs (miRNAs) contribute to the biological effects of Toll-like receptor (TLR) signaling on various cells. Our previous data showed that TLR9 signaling could enhance the growth and metastatic potential of human lung cancer cells. However, the potential role of miRNAs in the effects of TLR9 signaling on tumor biology remains unknown. In this paper, we first report that TLR9 signaling could reduce intrinsic miR-7 expression in human lung cancer cells. Furthermore, overexpression of miR-7 can significantly inhibit TLR9 signaling–enhanced growth and metastatic potential of lung cancer cells in vitro and in vivo. Notably, we identify phosphoinositide-3-kinase, regulatory subunit 3 (PIK3R3) as a novel target molecule of miR-7 in lung cancer cells by Western blotting and luciferase report assay. Further study shows that miR-7 inhibits the effects of TLR9 signaling on lung cancer cells through regulation of the PIK3R3/Akt pathway. These data suggest that miR-7 could act as a fine-tuner in regulating the biological effects of TLR9 signaling on human lung cancer cells, which might be helpful to the understanding of the potential role of miRNAs in TLR signaling effects on tumor biology.

scholarly journals Steroid-hormone receptors in cell lines and tumor biopsies of human lung cancer

1996 ◽  
Vol 67 (3) ◽  
pp. 357-364 ◽  
Author(s):  
Ulrich Kaiser ◽  
Jürgen Hofmann ◽  
Margret Schilli ◽  
Bärbel Wegmann ◽  
Uwe Klotz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Lines ◽  
Hormone Receptors ◽  
Human Lung ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors ◽  
Human Lung Cancer ◽  
Tumor Biopsies

scholarly journals Human Lung-Resident Macrophages Express and Are Targets of Thymic Stromal Lymphopoietin in the Tumor Microenvironment

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2012
Author(s):  
Mariantonia Braile ◽  
Alfonso Fiorelli ◽  
Daniela Sorriento ◽  
Rosa Maria Di Crescenzo ◽  
Maria Rosaria Galdiero ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Human Lung ◽  
Short Form ◽  
Biological Effects ◽  
Thymic Stromal Lymphopoietin ◽  
Human Lung Cancer ◽  
Blood Monocytes ◽  
Adaptive Immune Cells ◽  
Angiopoietin 2 ◽  
Cancer Tissues

Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine highly expressed by epithelial cells and several innate and adaptive immune cells. TSLP exerts its biological effects by binding to a heterodimeric complex composed of TSLP receptor (TSLPR) and IL-7Rα. In humans, there are two TSLP isoforms: the short form (sfTSLP), constitutively expressed, and the long form (lfTSLP), which is upregulated in inflammation. TSLP has been implicated in the induction and progression of several experimental and human cancers. Primary human lung macrophages (HLMs), monocyte-derived macrophages (MDMs), and peripheral blood monocytes consitutively expressed sfTSLP mRNA. Incubation of HLMs, MDMs, and monocytes with lipopolysaccharide (LPS) or IL-4, but not with IL-13, induced TSLP release from HLMs. LPS, but not IL-4 or IL-13, induced CXCL8 release from HLMs. LPS, IL-4 alone or in combination with IL-13, induced the expression of lfTSLP, but not of sfTSLP from HLMs. Preincubation of HLMs with IL-4, alone or in combination with IL-13, but not IL-13 alone, synergistically enhanced TSLP release from LPS-activated macrophages. By contrast, IL-4, alone or in combination with IL-13, inhibited LPS-induced CXCL8 release from HLMs. Immunoreactive TSLP was detected in lysates of HLMs, MDMs, and monocytes. Incubation of HLMs with TSLP induced the release of proinflammatory (TNF-α), angiogenic (VEGF-A, angiopoietin 2), and lymphangiogenic (VEGF-C) factors. TSLP, TSLPR, and IL-7Rα were expressed in intratumoral and peritumoral areas of human lung cancer. sfTSLP and lfTSLP mRNAs were differentially expressed in peritumoral and intratumoral lung cancer tissues. The TSLP system, expressed in HLMs, MDMs, and monocytes, could play a role in chronic inflammatory disorders including lung cancer.

Eradication of experimental brain metastases of human non-small cell lung cancer by macitentan, a dual antagonist of the endothelin A and B receptor, combined with paclitaxel.

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 92-92
Author(s):  
Masaki Hanibuchi ◽  
Sun-Jin Kim ◽  
Kenji Otsuka ◽  
Sho Tabata ◽  
Takuya Kuramoto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Biological Effects ◽  
Small Cell ◽  
Human Lung Cancer ◽  
Small Cell Lung ◽  
Endothelin A

92 Background: Treatment of patients with lung cancer brain metastases remains a major challenge because of the limited availability of standard therapy. Thus, the development of successful treatment options for these patients is mandatory. Recently, the endothelin axis was reported to be involved in cancer progression through its pleiotropic biological effects on cell survival, proliferation, invasion, and metastasis. Methods: In this study, we evaluated both the in vitro and in vivoeffects of macitentan, an orally bioavailable, dual endothelin A receptor and endothelin B receptor antagonist, as monotherapy, and in combination with paclitaxel. Results: In human non-small cell lung cancer PC-14 cells, macitentan treatment inhibited cell proliferation, corresponding with inhibition of Akt and p42/44 mitogen-activated protein kinase phosphorylation, and increased apoptosis. The combination of macitentan and paclitaxel resulted in the potentiation of all of these effects, suggesting that macitentan could enhance sensitivity to paclitaxel. Moreover, macitentan completely abrogated astrocyte-mediated protection of tumor cells against paclitaxel. In an experimental brain metastasis model of human lung cancer, the combination of macitentan and paclitaxel significantly inhibited the growth of brain metastasis and produced a striking survival prolongation of tumor-bearing mice. Conclusions: The endothelin A and B receptor blockade by macitentan could be a promising therapeutic strategy for brain metastases of non-small cell lung cancer.

scholarly journals The Role of TGF-β Signaling in Lung Cancer Associated with Idiopathic Pulmonary Fibrosis

2018 ◽  
Vol 19 (11) ◽  
pp. 3611 ◽  
Author(s):  
Akira Saito ◽  
Masafumi Horie ◽  
Patrick Micke ◽  
Takahide Nagase
Keyword(s):  
Lung Cancer ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Current Knowledge ◽  
Field Cancerization ◽  
Unknown Etiology ◽  
Dismal Prognosis ◽  
Increased Risk

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease of unknown etiology and dismal prognosis. IPF patients are known to have an increased risk of lung cancer and careful decision-making is required for the treatment of lung cancer associated with IPF. Transforming growth factor (TGF)-β signaling plays a central role in tissue fibrosis and tumorigenesis. TGF-β-mediated pathological changes that occur in IPF lung tissue may promote the process of field cancerization and provide the microenvironment favorable to cancer initiation and progression. This review summarizes the current knowledge related to IPF pathogenesis and explores the molecular mechanisms that underlie the occurrence of lung cancer in the background of IPF, with an emphasis on the multifaceted effects of TGF-β signaling.

scholarly journals Methylation-derived inflammatory measures and lung cancer risk and survival

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Naisi Zhao ◽  
Mengyuan Ruan ◽  
Devin C. Koestler ◽  
Jiayun Lu ◽  
Lucas A. Salas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Cancer Risk ◽  
Lung Cancer Risk ◽  
Smoking Status ◽  
Conditional Logistic Regression ◽  
Cox Proportional Hazards ◽  
Cancer Development ◽  
Cancer Etiology ◽  
Increased Risk

Abstract Background Examining immunity-related DNA methylation alterations in blood could help elucidate the role of the immune response in lung cancer etiology and aid in discovering factors that are key to lung cancer development and progression. In a nested, matched case–control study, we estimated methylation-derived NLR (mdNLR) and quantified DNA methylation levels at loci previously linked with circulating concentrations of C-reactive protein (CRP). We examined associations between these measures and lung cancer risk and survival. Results Using conditional logistic regression and further adjusting for BMI, batch effects, and a smoking-based methylation score, we observed a 47% increased risk of non-small cell lung cancer (NSCLC) for one standard deviation (SD) increase in mdNLR (n = 150 pairs; OR: 1.47, 95% CI 1.08, 2.02). Using a similar model, the estimated CRP Scores were inversely associated with risk of NSCLC (e.g., Score 1 OR: 0.57, 95% CI: 0.40, 0.81). Using Cox proportional hazards models adjusting for age, sex, smoking status, methylation-predicted pack-years, BMI, batch effect, and stage, we observed a 28% increased risk of dying from lung cancer (n = 145 deaths in 205 cases; HR: 1.28, 95% CI: 1.09, 1.50) for one SD increase in mdNLR. Conclusions Our study demonstrates that immunity status measured with DNA methylation markers is associated with lung cancer a decade or more prior to cancer diagnosis. A better understanding of immunity-associated methylation-based biomarkers in lung cancer development could provide insight into critical pathways.

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