Combat Lung Cancer Research Articles

Unveiling the antitumor synergy between pazopanib and metformin on lung cancer through suppressing p-Akt/ NF-κB/ STAT3/ PD-L1 signal pathway

Pazopanib, an inhibitor of the VEGF receptor tyrosine kinase, has demonstrated significant antitumor effects in lung cancer. However, its application as a standard treatment for this type of cancer is limited by its drug resistance and toxicity. Metformin has the potential to combat lung cancer by modifying the tumor’s immune microenvironment.In this study, we investigated the potential antitumor effects and the associated underlying molecular mechanisms of the combination of pazopanib and metformin in lung cancer. In vitro studies were conducted using the A549 and H460 lung cancer cell lines, whereas urethane-induced lung cancer-bearing mice were used for in vivo assessments. The urethane-induced mice received oral administration of pazopanib (50 mg/kg) and/or metformin (250 mg/kg) for a duration of 21 days.The results indicated that the MTT assay demonstrated a combined cytotoxic effect of the pazopanib/metformin combination in H460 and A549 cells, as evidenced by CI and DRI analyses. The observed increase in annexin V levels and the corresponding increase in Caspase-3 activity strongly suggest that this combination induced apoptosis.Furthermore, the pazopanib/metformin combination significantly inhibited the p-Akt/NF-κB/IL-6/STAT3, HIF1α/VEGF, and TLR2/TGF-β/PD-L1 pathways while also increasing CD8 expression in vivo. Immunohistochemical analysis revealed that these antitumor mechanisms were manifested by the suppression of the proliferation marker Ki67. In conclusion, these findings revealed that metformin augments the antitumor efficacy of pazopanib in lung cancer by simultaneously targeting proliferative, angiogenic, and immunogenic signaling pathways, metformin enhances the antitumor effectiveness of pazopanib in lung cancer, making it a promising therapeutic option for lung cancer.

Advancements in Oncology: Evolving Standards of Care and Personalized Treatment in Lung Cancer

Lung cancer remains a significant global health concern, impacting patients and healthcare systems alike. In recent years, substantial progress has been made in understanding the biology, diagnosis, and treatment of both small-cell and non-small-cell lung cancer (SCLC and NSCLC). This research paper synthesizes and reviews key findings from multiple studies published between 2007 and 2023, addressing various aspects of lung cancer researchThe studies covered in this review encompass a broad spectrum of topics, including systemic therapy, targeted treatments, genetic mutations, healthcare strategies, and patient outcomes. Notable highlights include the impact of EGFR tyrosine kinase inhibitors on NSCLC treatment, the role of nuclear factor erythroid 2-related factor 2 (NRF2) in lung adenocarcinoma, the utilization of large databases in radiation oncology research, and the importance of empathy in patient care.The paper also examines the latest developments in the molecular epidemiology of lung cancer, differences in lung cancer susceptibility among ethnic populations, and the implementation of multidisciplinary clinics for timely lung cancer care. It further delves into the significance of liquid biopsy in identifying genetic mutations for targeted therapies, the effect of ALK-positive cell percentage on the outcomes of Alectinib treatment, and the role of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in adjuvant therapy.Furthermore, this review assesses the impact of platinum-based chemotherapy on the survival of NSCLC patients and explores predictive factors, such as the VeriStrat test, in second-line therapy. The research also addresses the challenges and opportunities in the use of immune checkpoint inhibitors in advanced NSCLC, as well as the clinical utility of epidermal growth factor receptor (EGFR) testing in first-line therapy.In conclusion, this comprehensive review sheds light on the current state of lung cancer research, highlighting breakthroughs, challenges, and the potential for future advancements in the diagnosis and treatment of this life-threatening disease. The insights gathered from these diverse studies provide a valuable resource for clinicians, researchers, and healthcare providers in their efforts to combat lung cancer and improve patient outcomes.

Yeni Sentezlenen Potansiyel HIF İnhibitörlerinin Hipoksik Koşullarda Küçük Hücre Dışı Akciğer Kanseri Üzerindeki İnhibitör Etkilerinin Belirlenmesi

According to global estimates, there are 2.3 million new cases and 1.8 million fatalities due to lung cancer each year. Despite recent progress in diagnosis and treatment, persistent challenges highlight the urgent need for novel therapeutics and innovative approaches to combat lung cancer effectively. Accordingly, in the present study, we aimed to investigate the anticancer properties of potential inhibitors of HIF-1α, compound 7a and 7b. In the study, HTB-54 and BEAS-2B cell lines were used. MTT cell viability experiments were performed to determine the effect of newly synthesized HIF inhibitors 7a and 7b on cell viability under normoxic and hypoxic conditions. Quantitative expression levels of HIF1A were determined by real-time PCR approach. While the half maximum inhibitory concentration (IC50) of compound 7a in HTB-54 cells was 10.37 µM under normoxic conditions, it was found to be 10.63 µM under hypoxic conditions. The IC50 value of another HIF inhibitor 7b in HTB-54 cells was found to be 8.80 µM under normoxic conditions and 9.54 µM under hypoxic conditions. The expression level of HIF1A was found to be lower in cells exposed to compounds 7a and 7b under hypoxia compared to the control group. Conversely, in normoxia, HIF1A expression level in cells exposed to compound 7a increased 6.5-fold (p<0.0001) compared to the control group, while it was found to increase approximately 9-fold (p<0.0001) when exposed to 7b. Consequently, both compound 7a and 7b holds great promise for future therapeutic interventions to lung cancer.

Nanocarrier mediated co-delivery of phytochemicals and chemo-drugs: an emerging strategy to combat lung cancer in a systemic way

Nanocarrier mediated co-delivery of phytochemicals and chemo-drugs: an emerging strategy to combat lung cancer in a systemic way

Chitosan nanoparticles as a smart nanocarrier for gefitinib for tackling lung cancer: Design of experiment and in vitro cytotoxicity study

Due to its poor solubility and systemic side effects, gefitinib (Gef) has limited application in treatment of lung cancer. In this study, we used design of experiment (DOE) tools to gain the necessary knowledge for the synthesis of high-quality gefitinib loaded chitosan nanoparticles (Gef-CSNPs) capable of delivering and concentrating Gef at A549 cells, thereby increasing therapeutic effectiveness while decreasing adverse effects. The optimized Gef-CSNPs were characterized by SEM, TEM, DSC, XRD, and FTIR analyses. The optimized Gef-CSNPs had a particle size of 158±3.6 nm, an entrapment efficiency of 93±1.2 %, and a release of 97±0.6 % after 8 h. The in vitro cytotoxicity of the optimized Gef-CSNPs was found to be significantly higher than pure Gef (IC50 = 10.08 ± 0.76 μg/mL and IC50 = 21.65 ± 0.32 μg/mL), respectively. In the A549 human cell line, the optimized Gef-CSNPs formula outperformed pure Gef in terms of cellular uptake (3.286 ± 0.12 μg/mL and 1.777 ± 0.1 μg/mL) and apoptotic population (64.82 ± 1.25 % and 29.38 ± 1.11 %), respectively. These findings explain why researchers are so interested in using natural biopolymers to combat lung cancer, and they paint an optimistic picture of their potential as a promising tool in the fight against lung cancer.

Synergistic Effects of AgNPs and Biochar: A Potential Combination for Combating Lung Cancer and Pathogenic Bacteria.

The synthesis of reliable biological nanomaterials is a crucial area of study in nanotechnology. In this study, Emericella dentata was employed for the biosynthesis of AgNPs, which were then combined with synthesized biochar, a porous structure created through biomass pyrolysis. The synergistic effects of AgNPs and biochar were evaluated through the assessment of pro-inflammatory cytokines, anti-apoptotic gene expression, and antibacterial activity. Solid biosynthesized AgNPs were evaluated by XRD and SEM, with SEM images revealing that most of the AgNPs ranged from 10 to 80 nm, with over 70% being less than 40 nm. FTIR analysis indicated the presence of stabilizing and reducing functional groups in the AgNPs. The nanoemulsion's zeta potential, hydrodynamic diameter, and particle distribution index were found to be -19.6 mV, 37.62 nm, and 0.231, respectively. Biochar, on the other hand, did not have any antibacterial effects on the tested bacterial species. However, when combined with AgNPs, its antibacterial efficacy against all bacterial species was significantly enhanced. Furthermore, the combined material significantly reduced the expression of anti-apoptotic genes and pro-inflammatory cytokines compared to individual treatments. This study suggests that low-dose AgNPs coupled with biochar could be a more effective method to combat lung cancer epithelial cells and pathogenic bacteria compared to either substance alone.

Identification of Potent hDHODH Inhibitors for Lung Cancer via Virtual Screening of a Rationally Designed Small Combinatorial Library.

Cancer is characterized by altered cellular metabolism, and metabolic enzymes are considered as a promising target for anticancer therapy. Pyrimidine metabolism dysregulation is associated with various types of cancer, particularly lung cancer, which is one of the leading causes of cancer-related mortality worldwide. Recent studies have shown that small-cell lung cancer cells are particularly reliant on the pyrimidine biosynthesis pathway and are sensitive to its disruption. DHODH, the rate-limiting enzyme of the de novo pyrimidine production pathway, is essential in the production of RNA and DNA and is overexpressed in malignancies such as AML, skin cancer, breast cancer, and lung cancer, thereby highlighting DHODH as a viable target for developing drugs to combat lung cancer. Herein, rational drug design and computational techniques were used to discover novel DHODH inhibitors. A small combinatorial library was generated, and the top hits were synthesized and tested for anticancer activity against three lung cancer cell lines. Among the tested compounds, compound 5c possessed a stronger cytotoxicity (TC50 of 11 μM) compared to the standard FDA-approved drug (Regorafenib, TC50 of 13 μM) on the A549 cell line. Furthermore, compound 5c demonstrated potent inhibitory activity against hDHODH at a nanomolar level of 421 nM. DFT, molecular docking, molecular dynamic simulations, and free energy calculations were also carried out to understand the inhibitory mechanisms of the synthesized scaffolds. These in silico studies identified key mechanisms and structural features that will be crucial for future studies.

Integrated omics profiling and network pharmacology uncovers the prognostic genes and multi-targeted therapeutic bioactives to combat lung cancer

Non-small cell lung cancer (NSCLC) is the frequent subtype of lung cancer and the currently used treatment methods, diagnosis, and chemoresistance are relatively ineffective. Determining the pharmacological targets from active biomolecules of medicinal plants has become a frontiers era for biomedical research to develop novel therapies. In view of these scenarios, this pilot study, network pharmacology, cheminformatics, integrative omics, molecular docking and in vitro anti-cancer analysis were performed to unveil the multi-targeted treatment mechanisms of novel plant bioactives to treat lung cancer. Bioactive molecules from medicinal plants were compiled from PubChem. Network pharmacology approach revealed that 29 compounds efficiently target the 390 human and lung cancer associated genes. In addition, comparative analysis was performed and identified the 7 bioactive molecules significantly targeting 8 lung cancer genes. The integrative omics analysis discovered unique genes between the lung cancer and normal lung tissues. These genes were further validated through protein-protein interaction, gene ontology, gene functional and pathway enrichment, boxplot and overall survival analyses to understand the function of unique genes and their involvement in cancer signaling pathways. Survival heatmap analyses identified the significant prognostic genes. Docking results revealed that, lupeol and p-coumaric acid displayed high binding affinities with MIF, CCNB1, FABP4. Hence, we selected these two bioactives for in vitro analysis. Furthermore, these selected bioactives were showed concentration dependent cytotoxicity against the lung adenocarcinoma cells (A549). This holistic study has opened up novel avenues and unravels the cancer prognostic genes which could serve as druggable target and bioactives with anti-cancerous efficacy. Further functional validations are prerequisites to deciphering these bioactives as commercial drug candidates.

Bio-Mediated Zinc Oxide Nanoparticles through Tea Residue: Ecosynthesis, Characterizations, and Biological Efficiencies

Recent advances in nanotechnology have placed a major emphasis on environmentally friendly processes that encourage sustainable growth by using moderate reaction conditions and non-toxic precursors. In the present study, a simple, inventive, and affordable green technique was applied to generate bio-augmented ZnO nanoparticles using an aqueous extract of tea residue as a reducing and stabilizing component. Numerous methods, including UV-Vis, XRD, FT-IR, FE-SEM with EDAX and TEM were used to analyze ZnO nanoparticles that were generated. The antimicrobial capabilities of biomediated ZnO nanoparticles against pathogenic organisms were examined using an agar well method. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) and flow cytometry analysis was utilized to explore cytotoxic effects and apoptosis, and methylene blue dye was used to examine photocatalytic activity. The ZnO nanoparticles demonstrated considerable anticancer activity in human lung cancer cells (A549) as well as highly effective antibacterial activity against several different microbial pathogens. Furthermore, the greatest degradation percentage of methylene blue obtained was found to be 86% after 140 min. Therefore, it is concluded that the chosen nanoparticle combination enhanced antimicrobial, anticancer and photocatalytic activities. The combination may represent a useful tool for removing dye pollution from wastewater and, ideally, be used in the pharmaceutical sector to combat lung cancer.

Gefitinib-loaded starch nanoparticles for battling lung cancer: Optimization by full factorial design and in vitro cytotoxicity evaluation

Lung cancer is the number one killer among all cancer types. For decades, clinicians have been using conventional chemotherapeutics, but they can’t rely on them alone anymore, because they poison bad cells and good cells as well. Researchers exploited nanotechnology as a potential tool to develop a platform for drug delivery to improve therapeutic efficiency. A quality by design synthesis of gefitinib-loaded starch nanoparticles (Gef-StNPs) has emerged as an essential tool to study and optimize the factors included in their synthesis. Therefore, we applied design of experiment (DOE) tools to attain the essential knowledge for the synthesis of high-quality Gef-StNPs that can deliver and concentrate the gefitinib (Gef) at A549 cells, thereby improving therapeutic efficacy and minimizing adverse effects. The in vitro cytotoxicity after exposing the A549 human lung cancer cells to the optimized Gef-StNPs was found to be much higher than that of the pure Gef (IC50 = 6.037 ± 0.24 and 21.65 ± 0.32 μg/mL, respectively). The optimized Gef-StNPs formula showed superiority over the pure Gef regarding the cellular uptake in A549 human cell line (3.976 ± 0.14 and 1.777 ± 0.1 μg/mL) and apoptotic population (77.14 ± 1.43 and 29.38 ± 1.11 %), respectively. The results elucidate why researchers have a voracious appetite for using natural biopolymers to combat lung cancer and paint an optimistic picture of their potential to be a promising tool in battling lung cancer.

SAVED BY CLOSE FOLLOW-UP: A UNIQUE CASE OF RECURRENT SQUAMOUS CELL CARCINOMA OF THE LUNG MARKED FOR OBLITERATION

SAVED BY CLOSE FOLLOW-UP: A UNIQUE CASE OF RECURRENT SQUAMOUS CELL CARCINOMA OF THE LUNG MARKED FOR OBLITERATION

Targeting Nuclear Receptors in Lung Cancer-Novel Therapeutic Prospects.

Lung cancer, the second most commonly diagnosed cancer, is the major cause of fatalities worldwide for both men and women, with an estimated 2.2 million new incidences and 1.8 million deaths, according to GLOBOCAN 2020. Although various risk factors for lung cancer pathogenesis have been reported, controlling smoking alone has a significant value as a preventive measure. In spite of decades of extensive research, mechanistic cues and targets need to be profoundly explored to develop potential diagnostics, treatments, and reliable therapies for this disease. Nuclear receptors (NRs) function as transcription factors that control diverse biological processes such as cell growth, differentiation, development, and metabolism. The aberrant expression of NRs has been involved in a variety of disorders, including cancer. Deregulation of distinct NRs in lung cancer has been associated with numerous events, including mutations, epigenetic modifications, and different signaling cascades. Substantial efforts have been made to develop several small molecules as agonists or antagonists directed to target specific NRs for inhibiting tumor cell growth, migration, and invasion and inducing apoptosis in lung cancer, which makes NRs promising candidates for reliable lung cancer therapeutics. The current work focuses on the importance of various NRs in the development and progression of lung cancer and highlights the different small molecules (e.g., agonist or antagonist) that influence NR expression, with the goal of establishing them as viable therapeutics to combat lung cancer.

Development of a potential anti-cancer pulmonary nanosystem consisted of chitosan-doped LeciPlex loaded with resveratrol using a machine learning method

A novel self-assembled lecithin-based cationic nanocarrier (LeciPlex) doped with chitosan was prepared to improve Resveratrol solubility and anticancer efficacy. Using on a machine learning method based on regression analysis, LP5 (composed of lecithin, Peceol® and chitosan) was selected as the optimized one. This formula was spherical-shaped with a particle size of 59 nm, an encapsulation efficiency of 89% and a mean release time of 2.75 h together with a good mucoadhesive potential. Cascade impactor studies revealed the possible deep lung deposition of LP5 after nebulization. The safety of Resveratrol suspension and LP5 were checked on WISH cell line. Compared with Doxorubicin, both Resveratrol suspension and LP5 showed potent anticancer effects against the A549 cell line with IC50 values of 2.312, 2.200 and 1.708 μg/ml, respectively. These results indicated that the selected formula (LP5) significantly enhanced the crude drug anticancer effect by 63.2 fold and showed a higher anticancer selectivity index (>5.51). Furthermore, after 24 h, A549 up-took the LP5 more than the drug suspension by 40,000 fold. In addition, LP5 markedly induced the cellular apoptosis in A549 treated cells with a percentage of 73.1 compared to untreated cells. In conclusion, the results confirmed the enhanced lung anticancer effect, lower toxicity, and higher selectivity of the selected Resveratrol-loaded LeciPlex compared to the drug suspension. This study presents a potential nano-vesicular system for nebulization to combat lung cancer.

One-Pot Preparation of Ultra-Small Lipid-Polymer Nanoparticles Loaded with Cis-Platinum to Combat Lung Cancer

The cis-platinum (CDDP) is a first line chemotherapeutics drugs to combat lung cancer. However, its efficacy is largely limited due to the off-target delivery and multidrug resistance (MDR) upon in vivo applications. In order to solve this problem, here in our study, we prepared ultra-small lipidpolymer nanoparticles (USLPNPs) using one-pot method and to load CDDP (USLPNPs-CDDP) for the effective lung cancer therapy. Our results showed that the size of USLPNPs-CDDP was 20 nm and the stability of this platform was high. The sustained drug release afforded the long-lasting administration of CDDP to treat cancers. Most importantly, the USLPNPs-CDDP was able to bypass the CDDP resistance of A549/CDDP cells, which resulted in better anticancer benefits as compared to free CDDP both in vitro and in vivo.

Promise of gold nanomaterials as a lung cancer theranostic agent: a systematic review

Lung cancer is considered to be the second most prevalent form of cancer in the world and is associated with high mortality rates. Early diagnosis and targeted therapies for lung cancer can significantly extend patient survival. However, traditional strategies for lung cancer diagnosis lack sensitivity and selectivity. Additionally, available conventional drugs are losing their therapeutic potential due to side effects and the development of drug resistance. To overcome these drawbacks, there is an urgency to develop new potent theranostic agents to detect and combat cancer at an early stage. Recently, intensive progress has been made in the development and biomedical application of nanomaterials in cancer diagnosis, detection, and treatment. Gold nanomaterials (GNMs) have drawn considerable attention as a nano-theranostic agent due to their unique and tunable physical features. Therefore, this review aims to systematically analyze the efficiency of GNMs as a lung cancer theranostic agent. Published articles related to the study were selected from three popular electronic online databases including PubMed, Google Scholar, and Web of Science. Studied articles (n = 61) demonstrated that GNMs modified with photosensitive agents, miRNA, antibodies, peptides, conventional chemotherapeutic drugs, and other biomolecules improved the efficacy and efficiency of traditional diagnostic and therapeutic strategies to combat lung cancer. Surface-modified GNMs can be used as reliable, accurate, sensitive, and cheap lung cancer detection tools, as well as potent selective cytotoxic agents.

Current clinical trials and patent update on lung cancer: a retrospective review

Several clinical trials using different interventions are currently being sponsored to combat lung cancer at its different stages. The purpose of this study was to provide a portfolio of those trials. All active, open and recruiting clinical trials registered at ClinicalTrials.gov up to March 2018 were included. Information related to 6092 registered lung cancer trials was downloaded. Phase II trials were in the majority, comprising nearly 48.7% of total clinical trials with industry the major sponsor (41.3%) followed by NIH (12.3%). Multicenter studies were the norm accounting for 47.9% and the main study location was the USA (50.9%). Common interventions were radiation (26%), surgery (22%) and EGFR inhibitors (17%). Patent information includes major patent filing office and sponsors. The data analysis provides a comprehensive description of lung cancer trials.

MiR-21 regulates immunosuppression mediated by myeloid-derived suppressor cells by impairing RUNX1-YAP interaction in lung cancer

BackgroundMyeloid-derived suppressor cells (MDSCs) are known suppressors of antitumor immunity and contribute to immunosuppressive microenvironment during tumor development including lung cancer. Accumulating evidence shows microRNAs (miRNAs) affect tumor-expanded MDSC accumulation and function in tumor microenvironment and favor solid tumor growth. Herein, we aim to characterize the role of miR-21 in regulating the accumulation and activity of MDSCs in lung cancer.MethodsThe proportions of MDSCs, T helper cells (Th), and cytotoxic T lymphocytes (CTL) were evaluated by flow cytometric analyses of peripheral blood and tumor tissues collected from Lewis lung-cancer-bearing mice. T cell proliferation assay was performed in CD4+ or CD8+ T cells cocultured with MDSCs. MDSC apoptosis was examined by flow cytometric analysis. The levels of IL-10, TGF-β, and GM-CSF in mouse serum were determined by ELISA. miR-21 targeting RUNX1 and RUNX1 interaction with YAP were evaluated by RIP, dual-luciferase reporter gene, and ChIP assays.ResultsMiR-21 inhibition by its antagomir reduced the proportion of MDSCs, increased the proportion of Th and CTL in peripheral blood and tumor tissues of Lewis lung-cancer-bearing mice, protected Th and CTL from the suppression of MDSCs, increased apoptosis of MDSCs, but reduced IL-10, TGF-β and GM-CSF levels in mouse serum. RUNX1 could transcriptionally inhibit the YAP expression, whereas miR-21 targeting RUNX1 led to elevated YAP expression levels. Mechanistic investigation showed that miR-21 maintained MDSC accumulation in tumor microenvironment and promoted immunosuppressive ability of MDSCs in Lewis lung-cancer-bearing mice by down-regulating RUNX1and up-regulating YAP.ConclusionsTaken together, the study provides evidence that targeting miR-21 in MDSCs may be developed as an immunotherapeutic approach to combat lung cancer development.

Anti-tumor effect of PEG-coated PLGA nanoparticles of febuxostat on A549 non-small cell lung cancer cells.

In the present study, febuxostat (FBX)-loaded PEG-coated PLGA nanoparticles (FBX-PLGA-PEG) were developed and its anticancer activity on lung cancer cells was evaluated. FBX-PLGA-PEG were prepared by nanoprecipitation technique and characterized for particle size, size distribution, entrapment efficiency, and in vitro drug release study. The optimized formulations were used to evaluate cell viability, apoptosis, cell cycle, and caspase activity in A549 lung cancer cells. The optimized formulation showed spherical particle with average particle size of 180 ± 4.72nm, particle-size distribution 0.223 ± 0.003, entrapment efficiency (70 ± 2.56%), and drug release (99.1 ± 2.33%) at 12h. MTT cytotoxicity assay showed better cytotoxic potential of FBX-NPs than FBX solution against NSCLC A549 cells. The lower IC50 of FBX-NP (52.62 ± 2.52µg/mL) compared to FBX (68.0 ± 4.12µg/mL) are suggestive of a potential cytotoxic effect of nano-formulation compared to the drug itself. Furthermore, flow cytometry analysis showed significantly higher percentage of total apoptotic cells in FBX-NPs (10.38 ± 1.57%) as compared to FBX solution (2.76 ± 0.17%) showed strong proapoptotic potential of FBX nano-formulation. The increased caspase activity and percent of cells at G2/M phase of cell cycle increased for FBX nanoparticles were more effective than FBX solution in increasing caspase activity and percent of cells at G2/M phase of cell cycle. Our studies with FBX nanoparticles exhibited promising outcome which could be used as a strategies to combat lung cancer.

B24 The Role of Cigarette Smoke and miR520a in Pulmonary Frizzled 9 Expression

Lung cancer is the deadliest cancer, and for this reason treatment is highly researched. Alternatively, chemoprevention can be used to combat lung cancer in individuals who are at high risk of diagnosis, such as cigarette smokers. Frizzled 9 (Fzd9) is required in vitro for chemopreventive effects of iloprost, a prostacyclin analogue, in the lung. In non-small cell lung cancer (NSCLC) cell lines, Fzd9 activates PPARγ, leading to inhibition of transformed growth. Cigarette smoke exposure decreases Fzd9 expression. The goal of this study is to elucidate the relationship between cigarette smoke and miRNA regulation of Fzd9 expression. NSCLC cells exposed to cigarette smoke condensate (CSC) showed decreased Fzd9 3’ UTR activity, suggesting CSC regulates Fzd9 expression through miRNA. miRNA database analysis suggested miR-95, miR-106b, and miR-520a as potential regulators of Fzd9. Immortalized human bronchial epithelial cells (HBEC) and an Fzd9-positive NSCLC cell line (A549) transfected with miR-520a oligonucleotide mimic showed decreased Fzd9 3’UTR luciferase activity. miR-520a expression increased in HBEC and NSCLC cells after CSC exposure. We have tested a miR-520a inhibitor to use for future rescue experiments in an Fzd9-negative cell line (H322). Transient overexpression of miR-520a in HBEC and A549 did not affect cell viability or proliferation, so we made a stable miR-520a expressing HBEC line that we will use for longer-duration cell assays. miR-520a may play an important role in the regulation of Fzd9 by cigarette smoke, and future experiments will characterize this relationship and potentially impact the application of iloprost chemoprevention.

Emerging Theranostic Gold Nanomaterials to Combat Lung Cancer: A Systematic Review

Lung cancer remains the significant cause of deaths in males and females worldwide and many attempts have been made for diagnosis and treatment of lung cancer. Nanotechnology has emerged as a novel strategy to design smart nanostructure weapons to combat lung cancer. Recently, the biogenic gold nanoparticles (AuNPs) have attracted highlighted interest for lung cancer theranostics. The current systematic review served to evaluate the anticancer potential of biologically synthesized AuNPs against lung cancer cells through in vitro studies. We provided valuable information regarding the efficacy of biogenic AuNPs suggesting their potential for next generation of anticancer drugs. The articles were identified through international databases involving Cochrane, Web of Science, PubMed, Scopus, Science Direct, ProQuest, and Embase. Eighteen articles were found eligible to enter into the current study. Our findings represented that although some studies reported nontoxicity of biogenic AuNPs against lung cancer cells, most of the studies reported significant anticancer activity of these nanoparticles (NPs) against lung cancer cells. Although the in vitro studies provided preliminary evidence for lung anticancer potential of biogenic AuNPs, further in vivo investigations are required to confirm the efficacy of these NPs through animal models.