Development of syngeneic murine cell lines for use in immunocompetent orthotopic lung cancer models

Lung cancer, which remains a major cause of mortality worldwide, is a histologically diverse condition and demonstrates substantial phenotypic and genomic diversity among individual patients, manifesting as both intertumoral and intratumoral heterogeneity. This heterogeneity has made it difficult to develop lung cancer models. Two-dimensional (2D) cancer cell lines have been used to study genetic and molecular alterations in lung cancer. However, cancer cell lines have several disadvantages, including random genetic drift caused by long-term culture, a lack of annotated clinical data, and most importantly, the fact that only a subset of tumors shows 2D growth on plastic. Three-dimensional models of cancer have the potential to improve cancer research and drug development because they are more representative of cancer biology and its diverse pathophysiology. Herein, we present an integrated review of current information on preclinical lung cancer models and their limitations, including cancer cell line models, patient-derived xenografts, and lung cancer organoids, and discuss their possible therapeutic applications for drug discovery and screening to guide precision medicine in lung cancer research. Altogether, the success rate of generating lung cancer organoids must be improved, and a lung cancer organoid culture system is necessary to achieve the goal of designing an individualized therapeutic strategy for each lung cancer patient.

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Effects of chemical constituents from Fumaria indica on the production of cytokines & NO in LPS-stimulated murine cell lines

Planta Medica ◽

10.1055/s-0034-1382529 ◽

2014 ◽

Vol 80 (10) ◽

Cited By ~ 1

Author(s):

UC Agrahari ◽

SK Godasu ◽

KK Bhutani

Keyword(s):

Cell Lines ◽

Chemical Constituents ◽

Murine Cell

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3D Cultivation of Lung Cancer Cell Lines

10.1055/s-0037-1615331 ◽

2018 ◽

Author(s):

JR Seiz ◽

J Moyer ◽

A Menke

Keyword(s):

Lung Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Lung Cancer Cell ◽

3D Cultivation

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The Key microRNAs Regulated the Development of Non-small Cell Lung Cancer by Targeting TGF-β-induced epithelial–mesenchymal Transition

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190410151945 ◽

2019 ◽

Vol 22 (4) ◽

pp. 238-244 ◽

Cited By ~ 2

Author(s):

Gang Chen ◽

Bo Ye

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lines ◽

Cell Lung Cancer ◽

Small Cell ◽

Nsclc Cell ◽

Normal Lung ◽

Migration And Invasion ◽

Small Cell Lung ◽

Mesenchymal Transition

Purpose: Epithelial-to-Mesenchymal Transition (EMT) was reported to play a key role in the development of Non-Small Cell Lung Cancer (NSCLC). The process of EMT is regulated by the changes of miRNAs expression. However, it is still unknown which miRNA changed the most in the process of canceration and whether these changes played a role in tumor development. Methods: A total of 36 SCLC patients treated in our hospital between 11th, 2015 and 10th, 2017 were enrolled. The samples of cancer tissues and paracancer tissues of patients were collected and analyzed. Then, the miRNAs in normal lung cells and NSCLC cells were also analyzed. In the presence of TGF-β, we transfected the miRNA mimics or inhibitor into NSCLC cells to investigate the role of the significantly altered miRNAs in cell migration and invasion and in the process of EMT. Results: MiR-330-3p was significantly up-regulated in NSCLC cell lines and tissues and miRNA- 205 was significantly down-regulated in NSCLC cell lines and NSCLC tissues. Transfected miRNA-205 mimics or miRMA-330-3p inhibitor inhibited the migration and invasion of NCIH1975 cell and restrained TGF-β-induced EMT in NSCLC cells. Conclusion: miRNA-330-3p and miRNA-205 changed the most in the process of canceration in NSCLC. Furthermore, miR-330-3p promoted cell invasion and metastasis in NSCLC probably by promoting EMT and miR-205 could restrain NSCLC likely by suppressing EMT.

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Prediction of 10-year and lifetime risk of cancer in individual patients with established cardiovascular disease, results from UCC-SMART and CANTOS

European Heart Journal ◽

10.1093/ehjci/ehaa946.2815 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

C.C Van 't Klooster ◽

P.M Ridker ◽

N.R Cook ◽

J.G.J.V Aerts ◽

J Westerink ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Factors ◽

Lung Cancer ◽

Cancer Risk ◽

Prediction Models ◽

Funding Source ◽

Cancer Models ◽

Total Cancer ◽

The Cantos ◽

Risk Of Cancer

Abstract Background As treatment for cardiovascular disease (CVD) has improved substantially over the last decades, more patients survive acute CVD manifestations and are at risk for developing cancer as well as recurrent CVD. Due to similar risk factors, including smoking and obesity, patients with established CVD are at higher risk for cancer. Objectives The aim of this study was to develop and externally validate prediction models for the estimation of 10-year and lifetime risk for total, colorectal, and lung cancer in patients with established CVD. Methods Data from patients with established CVD from the UCC-SMART prospective cohort study (N=7,280) were used for model development, and data from the CANTOS trial (N=9,322) were used for model validation. Predictors were selected based on previously published cancer risk prediction models or cancer risk factors, easy clinical availability, and availability in the derivation dataset (UCC-SMART cohort). A Fine and Gray competing risk-adjusted lifetime model was developed for total, colorectal, and lung cancer. Results Selected predictors were age, sex, smoking status, weight, height, alcohol use, antiplatelet use, diabetes mellitus, and C-reactive protein. External calibration for 4-year risks of the total cancer, colorectal cancer, and lung cancer models was good (Figure 1), and C-statistics were 0.63–0.74 in the CANTOS trial population. Median predicted lifetime risks in CANTOS were 26% (range 1%-52%) for total cancer, 4% (range 0%-13%) for colorectal cancer, and 5% (range 0%-37%) for lung cancer. Conclusions Lifetime and 10-year risk of cancer can be estimated with easy to measure variables in patients with established CVD, showing a wide distribution of predicted lifetime risks for total cancer and lung cancer. Using these lifetime models in clinical practice could increase understanding of cancer risk and aid in emphasizing healthy lifestyle changes. Figure 1. Calibration plots of cancer models Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): University Medical Center; Additional funding: CANTOS trial was funded by Novartis Pharmaceuticals.

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Nicotine promotes the development of non-small cell lung cancer through activating LINC00460 and PI3K/Akt signaling

Bioscience Reports ◽

10.1042/bsr20182443 ◽

2019 ◽

Vol 39 (6) ◽

Cited By ~ 1

Author(s):

Hongying Zhao ◽

Yu Wang ◽

Xiubao Ren

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Cell Lines ◽

Akt Signaling ◽

Small Cell ◽

Nsclc Cell ◽

Expression Level ◽

In Vitro Experiments ◽

Small Cell Lung

Abstract Objective: Nicotine, the main ingredient in tobacco, is identified to facilitate tumorigenesis and accelerate metastasis in tumor. Studies in recent years have reported that long intergenic non-protein coding RNA 460 (LINC00460) is strongly associated with lung cancer poor prognosis and nicotine dependence. Nonetheless, it is unclear whether nicotine promotes the development of lung cancer through activation of LINC00460. Methods: We determined that LINC00460 expression in lung cancer tissues and the prognosis in patients with non-small cell lung carcinoma (NSCLC) using Gene Expression Profiling Interactive Analysis (GEPIA) website and The Cancer Genome Atlas (TCGA) database. Through in vitro experiments, we studied the effects of nicotine on LINC00460 in NSCLC cells lines using Cell Counting Kit-8 (CCK-8), transwell test, flow cytometry, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot assays. Results: We identified the significant up-regulated expression level of LINC00460 in NSCLC tissues and cell lines, especially, the negative correlation of LINC00460 expression level with overall survival (OS). In in vitro experiments, LINC00460 was overexpressed in NSCLC cell lines under nicotine stimulation. Nicotine could relieve the effect of LINC00460 knockdown on NSCLC cell proliferation, migration and apoptosis. The same influence was observed on PI3K/Akt signaling pathway. Conclusions: In summary, this is the first time to examine the potential roles of LINC00460 in lung cancer cell proliferation, migration and apoptosis induced by nicotine. This may help to develop novel therapeutic strategies for the prevention and treatment of metastatic tumors from cigarette smoke-caused lung cancer by blocking the nicotine-activated LINC00460 pathway.

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Gefitinib loaded PLGA and chitosan coated PLGA nanoparticles with magnified cytotoxicity against A549 Lung cancer cell Lines

Saudi Journal of Biological Sciences ◽

10.1016/j.sjbs.2021.05.025 ◽

2021 ◽

Author(s):

Abdullah S. Alshetaili

Keyword(s):

Lung Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Plga Nanoparticles ◽

Lung Cancer Cell ◽

A549 Lung Cancer Cell ◽

A549 Lung

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Small-molecule inhibition of APE1 induces apoptosis, pyroptosis, and necroptosis in non-small cell lung cancer

Cell Death and Disease ◽

10.1038/s41419-021-03804-7 ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Kaili Long ◽

Lili Gu ◽

Lulu Li ◽

Ziyu Zhang ◽

Enjie Li ◽

...

Keyword(s):

Lung Cancer ◽

Dna Damage ◽

Small Cell Lung Cancer ◽

Cell Lines ◽

Small Molecule ◽

Cell Lung Cancer ◽

Small Cell ◽

Nsclc Cell ◽

Molecular Compound ◽

Small Cell Lung

AbstractApurinic/apyrimidinic endonuclease 1 (APE1) plays a critical role in the base excision repair (BER) pathway, which is responsible for the excision of apurinic sites (AP sites). In non-small cell lung cancer (NSCLC), APE1 is highly expressed and associated with poor patient prognosis. The suppression of APE1 could lead to the accumulation of unrepaired DNA damage in cells. Therefore, APE1 is viewed as an important marker of malignant tumors and could serve as a potent target for the development of antitumor drugs. In this study, we performed a high-throughput virtual screening of a small-molecule library using the three-dimensional structure of APE1 protein. Using the AP site cleavage assay and a cell survival assay, we identified a small molecular compound, NO.0449-0145, to act as an APE1 inhibitor. Treatment with NO.0449-0145 induced DNA damage, apoptosis, pyroptosis, and necroptosis in the NSCLC cell lines A549 and NCI-H460. This inhibitor was also able to impede cancer progression in an NCI-H460 mouse model. Moreover, NO.0449-0145 overcame both cisplatin- and erlotinib-resistance in NSCLC cell lines. These findings underscore the importance of APE1 as a therapeutic target in NSCLC and offer a paradigm for the development of small-molecule drugs that target key DNA repair proteins for the treatment of NSCLC and other cancers.

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Predicting ROR1/BCL2 combination targeted therapy of small cell carcinoma of the lung

Cell Death and Disease ◽

10.1038/s41419-021-03855-w ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Walter Z. Wang ◽

Konstantin Shilo ◽

Joseph M. Amann ◽

Alyssa Shulman ◽

Mohammad Hojjat-Farsangi ◽

...

Keyword(s):

Lung Cancer ◽

Targeted Therapy ◽

Small Cell Lung Cancer ◽

Cell Lines ◽

Cell Lung Cancer ◽

Therapeutic Target ◽

Small Cell ◽

Orphan Receptor ◽

Small Cell Lung ◽

Sclc Patient

AbstractSmall cell lung cancer (SCLC) remains a deadly form of cancer, with a 5-year survival rate of less than 10 percent, necessitating novel therapies. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal protein that is emerging as a therapeutic target and is co-expressed with BCL2 in multiple tumor types due to microRNA coregulation. We hypothesize that ROR1-targeted therapy is effective in small cell lung cancer and synergizes with therapeutic BCL2 inhibition. Tissue microarrays (TMAs) and formalin-fixed paraffin-embedded (FFPE) SCLC patient samples were utilized to determine the prevalence of ROR1 and BCL2 expression in SCLC. Eight SCLC-derived cell lines were used to determine the antitumor activity of a small molecule ROR1 inhibitor (KAN0441571C) alone and in combination with the BCL2 inhibitor venetoclax. The Chou-Talalay method was utilized to determine synergy with the drug combination. ROR1 and BCL2 protein expression was identified in 93% (52/56) and 86% (48/56) of SCLC patient samples, respectively. Similarly, ROR1 and BCL2 were shown by qRT-PCR to have elevated expression in 79% (22/28) and 100% (28/28) of SCLC patient samples, respectively. KAN0441571C displayed efficacy in 8 SCLC cell lines, with an IC50 of 500 nM or less. Synergy as defined by a combination index of <1 via the Chou-Talalay method between KAN0441571C and venetoclax was demonstrated in 8 SCLC cell lines. We have shown that ROR1 inhibition is synergistic with BCL2 inhibition in SCLC models and shows promise as a novel therapeutic target in SCLC.

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Differential Effects of Combined ATR/WEE1 Inhibition in Cancer Cells

Cancers ◽

10.3390/cancers13153790 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3790

Author(s):

Gro Elise Rødland ◽

Sissel Hauge ◽

Grete Hasvold ◽

Lilli T. E. Bay ◽

Tine T. H. Raabe ◽

...

Keyword(s):

Lung Cancer ◽

Cell Viability ◽

Cancer Treatment ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Combined Treatment ◽

Cancer Cell Lines ◽

Variable Extent ◽

Synergistic Induction

Inhibitors of WEE1 and ATR kinases are considered promising for cancer treatment, either as monotherapy or in combination with chemo- or radiotherapy. Here, we addressed whether simultaneous inhibition of WEE1 and ATR might be advantageous. Effects of the WEE1 inhibitor MK1775 and ATR inhibitor VE822 were investigated in U2OS osteosarcoma cells and in four lung cancer cell lines, H460, A549, H1975, and SW900, with different sensitivities to the WEE1 inhibitor. Despite the differences in cytotoxic effects, the WEE1 inhibitor reduced the inhibitory phosphorylation of CDK, leading to increased CDK activity accompanied by ATR activation in all cell lines. However, combining ATR inhibition with WEE1 inhibition could not fully compensate for cell resistance to the WEE1 inhibitor and reduced cell viability to a variable extent. The decreased cell viability upon the combined treatment correlated with a synergistic induction of DNA damage in S-phase in U2OS cells but not in the lung cancer cells. Moreover, less synergy was found between ATR and WEE1 inhibitors upon co-treatment with radiation, suggesting that single inhibitors may be preferable together with radiotherapy. Altogether, our results support that combining WEE1 and ATR inhibitors may be beneficial for cancer treatment in some cases, but also highlight that the effects vary between cancer cell lines.

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