Interplay between Cellular and Molecular Inflammatory Mediators in Lung Cancer

Inflammation is a component of the tumor microenvironment and represents the 7th hallmark of cancer. Chronic inflammation plays a critical role in tumorigenesis. Tumor infiltrating inflammatory cells mediate processes associated with progression, immune suppression, promotion of neoangiogenesis and lymphangiogenesis, remodeling of extracellular matrix, invasion and metastasis, and, lastly, the inhibition of vaccine-induced antitumor T cell response. Accumulating evidence indicates a critical role of myeloid cells in the pathophysiology of human cancers. In contrast to the well-characterized tumor-associated macrophages (TAMs), the significance of granulocytes in cancer has only recently begun to emerge with the characterization of tumor-associated neutrophils (TANs). Recent studies show the importance of CD47 in the interaction with macrophages inhibiting phagocytosis and promoting the migration of neutrophils, increasing inflammation which can lead to recurrence and progression in lung cancer. Currently, therapies are targeted towards blocking CD47 and enhancing macrophage-mediated phagocytosis. However, antibody-based therapies may have adverse effects that limit its use

Calcitriol Inhibits the Proliferation of Triple-Negative Breast Cancer Cells through a Mechanism Involving the Proinflammatory Cytokines IL-1β and TNF-α

Triple-negative breast cancer (TNBC) is one of the most aggressive tumors, with poor prognosis and high metastatic capacity. The aggressive behavior may involve inflammatory processes characterized by deregulation of molecules related to the immunological responses in which interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are involved. It is known that calcitriol, the active vitamin D metabolite, modulates the synthesis of immunological mediators; however, its role in the regulation of IL-1β and TNF-α in TNBC has been scarcely studied. In the present study, we showed that TNBC cell lines SUM-229PE and HCC1806 expressed vitamin D, IL-1β, and TNF-α receptors. Moreover, calcitriol, its analogue EB1089, IL-1β, and TNF-α inhibited cell proliferation. In addition, we showed that synthesis of both IL-1β and TNF-α was stimulated by calcitriol and its analogue. Interestingly, the antiproliferative activity of calcitriol was significantly abrogated when the cells were treated with anti-IL-1β receptor 1 (IL-1R1) and anti-TNF-α receptor type 1 (TNFR1) antibodies. Furthermore, the combination of calcitriol with TNF-α resulted in a greater antiproliferative effect than either agent alone, in the two TNBC cell lines and an estrogen receptor-positive cell line. In summary, this study demonstrated that calcitriol exerted its antiproliferative effects in part by inducing the synthesis of IL-1β and TNF-α through IL-1R1 and TNFR1, respectively, in TNBC cells, highlighting immunomodulatory and antiproliferative functions of calcitriol in TNBC tumors

Curcumin inhibits activation induced by urban particulate material or titanium dioxide nanoparticles in primary human endothelial cells - Fig 6

<p><b>Effect of curcumin on oxidative stress induced by PM</b>_<b>10</b><b>(A) and TiO</b>_<b>2</b><b>-NPs (B)</b>. Cells were treated with curcumin at 1 (C1), 10 (C10) and 100 (C100) μM alone or in combination with 3 and 10 μg/cm² of PM₁₀ and TiO₂-NPs (3) and (10) for 1 h. H₂O₂ (500 μM) was used as a positive control. Curcumin was added 1 h before the addition of PM₁₀ or TiO₂-NPs. Oxidative stress was evaluated by H₂DCF oxidation by flow cytometry. Data were expressed as percentage of H₂DCF oxidation with respect to control (100%) and shown as mean ± standard deviation (SD) of three separate experiments. p < 0.05, experiments compared with untreated cells (Control) (*) and with TiO₂-NPs or PM₁₀ alone (&).</p

Association between CD47 expression, clinical characteristics and prognosis in patients with advanced non-small cell lung cancer

Objective CD47 is an antiphagocytic molecule that contributes to tumor cell resistance in host immune surveillance. CD47 overexpression correlated with tumor progression and shorter survival in lung cancer. However, the expression and functional significance of CD47 in Non‐Small Cell Lung Cancer (NSCLC) has not been completely understood. Materials and Methods In this retrospective study, CD47 expression was immunohistochemically examined in tumor biopsies from 169 NSCLC patients. The association of CD47 levels (H‐score) with clinicopathological characteristics and survival outcomes was evaluated. Results CD47 protein was detected in 84% of patients with a median expression of 80% (0‐100). Tumor CD47 levels above 1% and 50% were found in 84% and 65.7% of patients, respectively. While, median CD47 staining index was 160 (0‐300). Patients were divided into two groups according to CD47 expression (high or low), using a cutoff value of 150. High CD47 expression was associated with wood smoke exposure (71.1% vs 28.9%, P = .013) and presence of EGFR (+) mutations (66.7% vs 33.3%, P = .04). Survival analysis carried out in the whole population did not show any association of CD47 expression and survival outcome. However, in patients with EGFR (+) mutations, CD47 expression was associated with higher progression‐free survival (PFS) (12.2 vs. 4.4 months, P = .032). When the survival analysis was performed according to CD47 levels (cut off value: 150), both, PFS and overall survival (OS) were shortened in patients with a high expression of CD47 (10.7 vs. NR, P = .156) and (29.2 vs. NR months P = .023), respectively. Conclusions CD47 overexpression is not a prognostic factor for PFS and OS in NSCLC patients. However, the presence of EGFR mutations and high expression of CD47 were associated with shortened PFS and OS. Coexpression of these markers represents a potential biomarker and characterizes a therapeutic niche for lung cancer

Effect of curcumin on the expression of early adhesion molecules induced by TiO₂-NPs.

<p>A) Top panel: E-selectin, B) Bottom panel: P-selectin. Cells were treated with curcumin at 1 (C1), 10 (C10) and 100 (C100) μM alone or in combination with 3 and 10 μg/cm² of TiO₂-NPs (3) and (10) for 3 h. The expression of early adhesion molecules was evaluated by flow cytometry. Curcumin was added 1 h before the addition of TiO₂-NPs. TNF- α (10 ng/mL) was used as positive control. The left side shows histograms of a representative experiment. Continuous lines correspond to control cells and dashed lines to treated cells. The right side shows data as mean ± standard deviation (SD) of three separate experiments, expressed as percentage of fluorescence in comparison with positive control (100%). p < 0.05, experiments compared with untreated cells (Control) (*) and with TiO₂-NPs alone (&).</p

Curcumin abolished some pro-inflammatory events induced by nanoparticles and particulate matter in endothelial cells.

<p>Inflammatory events such as the increase of monocytes adhesion, the expression of early and late adhesion molecules and oxidative stress are induced in endothelial cells exposed to PMs and TiO₂-NPs (A); however, pre-treatment with curcumin 1 h before the addition of particles, attenuate these events (B), indicating an anti-inflammatory and anti-oxidant role of curcumin.</p

Effect of curcumin on the expression of early adhesion molecules induced by PM₁₀.

<p>A) Top panel: E-selectin, B) Bottom panel: P-selectin. Cells were treated with curcumin at 1 (C1), 10 (C10) and 100 (C100) μM alone or in combination with 3 and 10 μg/cm² of PM₁₀ (3) and (10) for 3 h. The expression of early adhesion molecules was evaluated by flow cytometry. Curcumin was added 1 h before the addition of PM₁₀. TNF-α (10 ng/mL) was used as positive control. The left side shows histograms of a representative experiment. Continuous lines correspond to control cells and dashed lines to treated cells. The right side shows data as mean ± standard deviation (SD) of three separate experiments, expressed as percentage of fluorescence in comparison with control (100%). p < 0.05, experiments compared with untreated cells (Control) (*) and with PM₁₀ alone (&).</p

Effect of curcumin on the expression of late adhesion molecules induced by PM₁₀.

<p>A) Top panel ICAM-1, B) Middle panel: PECAM-1, C) Bottom panel: VCAM-1. Cells were treated with curcumin at 1 (C1), 10 (C10) and 100 (C100) μM alone or in combination with 3 and 10 μg/cm² of PM₁₀ (3) and (10) for 24 h. The expression of late adhesion molecules was evaluated by flow cytometry. Curcumin was added 1 h before the addition of PM₁₀. TNF-α (10 ng/mL) was used as positive control. The left side shows histograms of a representative experiment. Continuous lines correspond to control cells and dashed lines to treated cells. The right side shows data as mean ± standard deviation (SD) of three separate experiments, expressed as percentage of fluorescence in comparison with positive control (100%). p < 0.05, experiments compared with untreated cells (Control) (*) and with PM₁₀ alone (&).</p